<?xml version="1.0" encoding="UTF-8"?>

<!--XBRL Document Created with the Workiva Platform-->
<!--Copyright 2024 Workiva-->
<!--r:7b831019-61b0-4248-a5e7-14222ec80679,g:1082a7f9-1d5e-45df-8abf-7cd45795e4da-->
<link:linkbase xmlns:link="http://www.xbrl.org/2003/linkbase" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xmlns:xbrldt="http://xbrl.org/2005/xbrldt" xsi:schemaLocation="http://www.xbrl.org/2003/linkbase http://www.xbrl.org/2003/xbrl-linkbase-2003-12-31.xsd">
  <link:arcroleRef arcroleURI="http://xbrl.org/int/dim/arcrole/all" xlink:type="simple" xlink:href="http://www.xbrl.org/2005/xbrldt-2005.xsd#all"/>
  <link:arcroleRef arcroleURI="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:type="simple" xlink:href="http://www.xbrl.org/2005/xbrldt-2005.xsd#hypercube-dimension"/>
  <link:arcroleRef arcroleURI="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:type="simple" xlink:href="http://www.xbrl.org/2005/xbrldt-2005.xsd#dimension-default"/>
  <link:arcroleRef arcroleURI="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:type="simple" xlink:href="http://www.xbrl.org/2005/xbrldt-2005.xsd#dimension-domain"/>
  <link:arcroleRef arcroleURI="http://xbrl.org/int/dim/arcrole/domain-member" xlink:type="simple" xlink:href="http://www.xbrl.org/2005/xbrldt-2005.xsd#domain-member"/>
  <link:roleRef roleURI="http://www.esperion.com/role/CondensedStatementsofOperationsandComprehensiveIncomeLoss" xlink:type="simple" xlink:href="espr-20240331.xsd#CondensedStatementsofOperationsandComprehensiveIncomeLoss"/>
  <link:definitionLink xlink:role="http://www.esperion.com/role/CondensedStatementsofOperationsandComprehensiveIncomeLoss" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StatementLineItems_08539f87-615e-4553-8be1-6fb79469fa46" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_StatementLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StatementTable_5fc27ed3-88ff-48a2-948c-5b08d6da9268" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_StatementTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_StatementLineItems_08539f87-615e-4553-8be1-6fb79469fa46" xlink:to="loc_us-gaap_StatementTable_5fc27ed3-88ff-48a2-948c-5b08d6da9268" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductOrServiceAxis_28ca37f8-06e9-4c56-8d10-3f207a559759" xlink:href="https://xbrl.fasb.org/srt/2023/elts/srt-2023.xsd#srt_ProductOrServiceAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_StatementTable_5fc27ed3-88ff-48a2-948c-5b08d6da9268" xlink:to="loc_srt_ProductOrServiceAxis_28ca37f8-06e9-4c56-8d10-3f207a559759" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductsAndServicesDomain_28ca37f8-06e9-4c56-8d10-3f207a559759_default" xlink:href="https://xbrl.fasb.org/srt/2023/elts/srt-2023.xsd#srt_ProductsAndServicesDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_ProductOrServiceAxis_28ca37f8-06e9-4c56-8d10-3f207a559759" xlink:to="loc_srt_ProductsAndServicesDomain_28ca37f8-06e9-4c56-8d10-3f207a559759_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductsAndServicesDomain_3a846718-126a-412d-9893-961d8b1da08b" xlink:href="https://xbrl.fasb.org/srt/2023/elts/srt-2023.xsd#srt_ProductsAndServicesDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_ProductOrServiceAxis_28ca37f8-06e9-4c56-8d10-3f207a559759" xlink:to="loc_srt_ProductsAndServicesDomain_3a846718-126a-412d-9893-961d8b1da08b" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ProductMember_36e6348b-8dec-4d4c-b00f-04e3496156ca" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ProductMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ProductsAndServicesDomain_3a846718-126a-412d-9893-961d8b1da08b" xlink:to="loc_us-gaap_ProductMember_36e6348b-8dec-4d4c-b00f-04e3496156ca" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_CollaborationRevenueMember_617ab8cb-fc05-4b63-ad0e-ff71aa4727d8" xlink:href="espr-20240331.xsd#espr_CollaborationRevenueMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ProductsAndServicesDomain_3a846718-126a-412d-9893-961d8b1da08b" xlink:to="loc_espr_CollaborationRevenueMember_617ab8cb-fc05-4b63-ad0e-ff71aa4727d8" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RevenuesAbstract_0b43fc3e-f36d-4172-8399-7e0af4f17ae2" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_RevenuesAbstract"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_08539f87-615e-4553-8be1-6fb79469fa46" xlink:to="loc_us-gaap_RevenuesAbstract_0b43fc3e-f36d-4172-8399-7e0af4f17ae2" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax_bc893dcd-9c2b-4fac-84a8-fa7d29a72b22" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_RevenuesAbstract_0b43fc3e-f36d-4172-8399-7e0af4f17ae2" xlink:to="loc_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax_bc893dcd-9c2b-4fac-84a8-fa7d29a72b22" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OperatingExpensesAbstract_ffff4539-6342-4c0a-a0f3-dd477fce19df" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_OperatingExpensesAbstract"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_08539f87-615e-4553-8be1-6fb79469fa46" xlink:to="loc_us-gaap_OperatingExpensesAbstract_ffff4539-6342-4c0a-a0f3-dd477fce19df" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OtherCostAndExpenseOperating_66496d32-c2b9-42ef-b74a-9e4a559ca4ed" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_OtherCostAndExpenseOperating"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_OperatingExpensesAbstract_ffff4539-6342-4c0a-a0f3-dd477fce19df" xlink:to="loc_us-gaap_OtherCostAndExpenseOperating_66496d32-c2b9-42ef-b74a-9e4a559ca4ed" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ResearchAndDevelopmentExpenseExcludingAcquiredInProcessCost_73754fcb-f3c3-4c21-a826-d98c028b866d" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ResearchAndDevelopmentExpenseExcludingAcquiredInProcessCost"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_OperatingExpensesAbstract_ffff4539-6342-4c0a-a0f3-dd477fce19df" xlink:to="loc_us-gaap_ResearchAndDevelopmentExpenseExcludingAcquiredInProcessCost_73754fcb-f3c3-4c21-a826-d98c028b866d" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SellingGeneralAndAdministrativeExpense_f0123330-64c4-4340-b30f-8542bd98b118" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_SellingGeneralAndAdministrativeExpense"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_OperatingExpensesAbstract_ffff4539-6342-4c0a-a0f3-dd477fce19df" xlink:to="loc_us-gaap_SellingGeneralAndAdministrativeExpense_f0123330-64c4-4340-b30f-8542bd98b118" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OperatingExpenses_58b87736-c03b-43f7-9839-e69665d61c05" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_OperatingExpenses"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_OperatingExpensesAbstract_ffff4539-6342-4c0a-a0f3-dd477fce19df" xlink:to="loc_us-gaap_OperatingExpenses_58b87736-c03b-43f7-9839-e69665d61c05" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OperatingIncomeLoss_bec6a8f2-2812-4971-92cd-e4f6508da4aa" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_OperatingIncomeLoss"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_08539f87-615e-4553-8be1-6fb79469fa46" xlink:to="loc_us-gaap_OperatingIncomeLoss_bec6a8f2-2812-4971-92cd-e4f6508da4aa" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_InterestExpense_0e40f998-b501-4f8f-98a5-98eb783cb3a4" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_InterestExpense"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_08539f87-615e-4553-8be1-6fb79469fa46" xlink:to="loc_us-gaap_InterestExpense_0e40f998-b501-4f8f-98a5-98eb783cb3a4" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OtherNonoperatingIncomeExpense_453c5d26-d604-4cd7-bca7-8ca5954f74d3" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_OtherNonoperatingIncomeExpense"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_08539f87-615e-4553-8be1-6fb79469fa46" xlink:to="loc_us-gaap_OtherNonoperatingIncomeExpense_453c5d26-d604-4cd7-bca7-8ca5954f74d3" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_NetIncomeLoss_e7304986-0fab-47bf-979e-9607f9bb2e37" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_NetIncomeLoss"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_08539f87-615e-4553-8be1-6fb79469fa46" xlink:to="loc_us-gaap_NetIncomeLoss_e7304986-0fab-47bf-979e-9607f9bb2e37" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EarningsPerShareBasic_d4823ccb-4c72-459b-9e74-d49686be6699" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_EarningsPerShareBasic"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_08539f87-615e-4553-8be1-6fb79469fa46" xlink:to="loc_us-gaap_EarningsPerShareBasic_d4823ccb-4c72-459b-9e74-d49686be6699" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EarningsPerShareDiluted_f62df07d-f40c-4dba-b442-b3c6a9fdf208" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_EarningsPerShareDiluted"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_08539f87-615e-4553-8be1-6fb79469fa46" xlink:to="loc_us-gaap_EarningsPerShareDiluted_f62df07d-f40c-4dba-b442-b3c6a9fdf208" xlink:type="arc" order="7"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_WeightedAverageNumberOfSharesOutstandingBasic_11d893eb-1d87-4052-a634-408bb7f2cfd1" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_WeightedAverageNumberOfSharesOutstandingBasic"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_08539f87-615e-4553-8be1-6fb79469fa46" xlink:to="loc_us-gaap_WeightedAverageNumberOfSharesOutstandingBasic_11d893eb-1d87-4052-a634-408bb7f2cfd1" xlink:type="arc" order="8"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_WeightedAverageNumberOfDilutedSharesOutstanding_16dc3cb1-2dd9-4cc3-8631-7f3e17e42254" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_WeightedAverageNumberOfDilutedSharesOutstanding"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_08539f87-615e-4553-8be1-6fb79469fa46" xlink:to="loc_us-gaap_WeightedAverageNumberOfDilutedSharesOutstanding_16dc3cb1-2dd9-4cc3-8631-7f3e17e42254" xlink:type="arc" order="9"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OtherComprehensiveIncomeLossNetOfTaxPeriodIncreaseDecreaseAbstract_915dcff6-e4cb-474f-8cc7-d18f22ef87c2" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_OtherComprehensiveIncomeLossNetOfTaxPeriodIncreaseDecreaseAbstract"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_08539f87-615e-4553-8be1-6fb79469fa46" xlink:to="loc_us-gaap_OtherComprehensiveIncomeLossNetOfTaxPeriodIncreaseDecreaseAbstract_915dcff6-e4cb-474f-8cc7-d18f22ef87c2" xlink:type="arc" order="10"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent_625a15e9-4a2e-4d03-a4a1-9d694fca426c" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_OtherComprehensiveIncomeLossNetOfTaxPeriodIncreaseDecreaseAbstract_915dcff6-e4cb-474f-8cc7-d18f22ef87c2" xlink:to="loc_us-gaap_OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent_625a15e9-4a2e-4d03-a4a1-9d694fca426c" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ComprehensiveIncomeNetOfTax_e091edd2-b9cd-4fcd-8146-1f7ebba7c3d1" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ComprehensiveIncomeNetOfTax"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_08539f87-615e-4553-8be1-6fb79469fa46" xlink:to="loc_us-gaap_ComprehensiveIncomeNetOfTax_e091edd2-b9cd-4fcd-8146-1f7ebba7c3d1" xlink:type="arc" order="11"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.esperion.com/role/CondensedStatementsofStockholdersDeficit" xlink:type="simple" xlink:href="espr-20240331.xsd#CondensedStatementsofStockholdersDeficit"/>
  <link:definitionLink xlink:role="http://www.esperion.com/role/CondensedStatementsofStockholdersDeficit" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StatementLineItems_e88aeb4c-92fa-4f36-9d9f-dee39f614345" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_StatementLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StatementTable_3dd544ab-f837-434b-81a8-1b5997a0f262" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_StatementTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_StatementLineItems_e88aeb4c-92fa-4f36-9d9f-dee39f614345" xlink:to="loc_us-gaap_StatementTable_3dd544ab-f837-434b-81a8-1b5997a0f262" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StatementEquityComponentsAxis_7965c685-0d8d-49f5-85d0-c641bf49b01d" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_StatementEquityComponentsAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_StatementTable_3dd544ab-f837-434b-81a8-1b5997a0f262" xlink:to="loc_us-gaap_StatementEquityComponentsAxis_7965c685-0d8d-49f5-85d0-c641bf49b01d" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EquityComponentDomain_7965c685-0d8d-49f5-85d0-c641bf49b01d_default" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_EquityComponentDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_StatementEquityComponentsAxis_7965c685-0d8d-49f5-85d0-c641bf49b01d" xlink:to="loc_us-gaap_EquityComponentDomain_7965c685-0d8d-49f5-85d0-c641bf49b01d_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EquityComponentDomain_7dbaa1cd-1219-4e8f-bde2-f399bc8bb62e" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_EquityComponentDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_StatementEquityComponentsAxis_7965c685-0d8d-49f5-85d0-c641bf49b01d" xlink:to="loc_us-gaap_EquityComponentDomain_7dbaa1cd-1219-4e8f-bde2-f399bc8bb62e" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CommonStockMember_3c7ba36c-d440-4d42-ac56-d722360d5e37" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_CommonStockMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_EquityComponentDomain_7dbaa1cd-1219-4e8f-bde2-f399bc8bb62e" xlink:to="loc_us-gaap_CommonStockMember_3c7ba36c-d440-4d42-ac56-d722360d5e37" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AdditionalPaidInCapitalMember_fd481509-f7e9-4e38-a7c0-3fd57fae572b" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_AdditionalPaidInCapitalMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_EquityComponentDomain_7dbaa1cd-1219-4e8f-bde2-f399bc8bb62e" xlink:to="loc_us-gaap_AdditionalPaidInCapitalMember_fd481509-f7e9-4e38-a7c0-3fd57fae572b" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RetainedEarningsMember_9b262a44-8ab6-4830-807d-4a6d8e36caca" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_RetainedEarningsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_EquityComponentDomain_7dbaa1cd-1219-4e8f-bde2-f399bc8bb62e" xlink:to="loc_us-gaap_RetainedEarningsMember_9b262a44-8ab6-4830-807d-4a6d8e36caca" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AccumulatedOtherComprehensiveIncomeMember_e343d354-a1ef-41d6-896d-d954b975bbb4" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_AccumulatedOtherComprehensiveIncomeMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_EquityComponentDomain_7dbaa1cd-1219-4e8f-bde2-f399bc8bb62e" xlink:to="loc_us-gaap_AccumulatedOtherComprehensiveIncomeMember_e343d354-a1ef-41d6-896d-d954b975bbb4" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_TreasuryStockCommonMember_95f56e61-9b76-4dea-81ac-645945451931" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_TreasuryStockCommonMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_EquityComponentDomain_7dbaa1cd-1219-4e8f-bde2-f399bc8bb62e" xlink:to="loc_us-gaap_TreasuryStockCommonMember_95f56e61-9b76-4dea-81ac-645945451931" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_2da2f3e5-63d9-4ce8-9960-53f87f4b86e4" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_IncreaseDecreaseInStockholdersEquityRollForward"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_e88aeb4c-92fa-4f36-9d9f-dee39f614345" xlink:to="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_2da2f3e5-63d9-4ce8-9960-53f87f4b86e4" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SharesOutstanding_85ca0f60-a1e1-4ea5-ac48-53f9814d6f99" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_SharesOutstanding"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_2da2f3e5-63d9-4ce8-9960-53f87f4b86e4" xlink:to="loc_us-gaap_SharesOutstanding_85ca0f60-a1e1-4ea5-ac48-53f9814d6f99" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StockholdersEquity_ec2a18b3-80dd-4446-b251-68522719bef2" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_StockholdersEquity"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_2da2f3e5-63d9-4ce8-9960-53f87f4b86e4" xlink:to="loc_us-gaap_StockholdersEquity_ec2a18b3-80dd-4446-b251-68522719bef2" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StockIssuedDuringPeriodSharesRestrictedStockAwardGross_1c2fafa8-21b3-449e-a811-39cfe1e27c44" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_StockIssuedDuringPeriodSharesRestrictedStockAwardGross"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_2da2f3e5-63d9-4ce8-9960-53f87f4b86e4" xlink:to="loc_us-gaap_StockIssuedDuringPeriodSharesRestrictedStockAwardGross_1c2fafa8-21b3-449e-a811-39cfe1e27c44" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StockIssuedDuringPeriodValueRestrictedStockAwardGross_011397be-c036-4b54-b911-65ade2f6f788" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_StockIssuedDuringPeriodValueRestrictedStockAwardGross"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_2da2f3e5-63d9-4ce8-9960-53f87f4b86e4" xlink:to="loc_us-gaap_StockIssuedDuringPeriodValueRestrictedStockAwardGross_011397be-c036-4b54-b911-65ade2f6f788" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StockIssuedDuringPeriodSharesEmployeeStockPurchasePlans_3c1751af-085d-4a46-b62f-e95c7c8fcea3" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_StockIssuedDuringPeriodSharesEmployeeStockPurchasePlans"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_2da2f3e5-63d9-4ce8-9960-53f87f4b86e4" xlink:to="loc_us-gaap_StockIssuedDuringPeriodSharesEmployeeStockPurchasePlans_3c1751af-085d-4a46-b62f-e95c7c8fcea3" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StockIssuedDuringPeriodValueEmployeeStockPurchasePlan_36ed42fa-f1b0-477f-8021-e392f20406a6" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_StockIssuedDuringPeriodValueEmployeeStockPurchasePlan"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_2da2f3e5-63d9-4ce8-9960-53f87f4b86e4" xlink:to="loc_us-gaap_StockIssuedDuringPeriodValueEmployeeStockPurchasePlan_36ed42fa-f1b0-477f-8021-e392f20406a6" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue_78a467b4-cc00-4027-944b-05d63d06803d" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_2da2f3e5-63d9-4ce8-9960-53f87f4b86e4" xlink:to="loc_us-gaap_AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue_78a467b4-cc00-4027-944b-05d63d06803d" xlink:type="arc" order="7"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_StockAndWarrantsIssuedDuringPeriodSharesNewIssues_4164d4e7-8c59-449b-93f4-685020bcb1ee" xlink:href="espr-20240331.xsd#espr_StockAndWarrantsIssuedDuringPeriodSharesNewIssues"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_2da2f3e5-63d9-4ce8-9960-53f87f4b86e4" xlink:to="loc_espr_StockAndWarrantsIssuedDuringPeriodSharesNewIssues_4164d4e7-8c59-449b-93f4-685020bcb1ee" xlink:type="arc" order="8"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_StockAndWarrantsIssuedDuringPeriodValueNewIssues_d3b1c4e4-e2d3-4155-8264-3618678d4540" xlink:href="espr-20240331.xsd#espr_StockAndWarrantsIssuedDuringPeriodValueNewIssues"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_2da2f3e5-63d9-4ce8-9960-53f87f4b86e4" xlink:to="loc_espr_StockAndWarrantsIssuedDuringPeriodValueNewIssues_d3b1c4e4-e2d3-4155-8264-3618678d4540" xlink:type="arc" order="9"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_StockIssuedDuringPeriodSharesWarrantExercises_2be9aa2d-7b9e-4200-8f53-8246cce5f47c" xlink:href="espr-20240331.xsd#espr_StockIssuedDuringPeriodSharesWarrantExercises"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_2da2f3e5-63d9-4ce8-9960-53f87f4b86e4" xlink:to="loc_espr_StockIssuedDuringPeriodSharesWarrantExercises_2be9aa2d-7b9e-4200-8f53-8246cce5f47c" xlink:type="arc" order="10"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_StockIssuedDuringPeriodValueWarrantExercises_9be2129c-2a41-4384-a3fe-3001331eb110" xlink:href="espr-20240331.xsd#espr_StockIssuedDuringPeriodValueWarrantExercises"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_2da2f3e5-63d9-4ce8-9960-53f87f4b86e4" xlink:to="loc_espr_StockIssuedDuringPeriodValueWarrantExercises_9be2129c-2a41-4384-a3fe-3001331eb110" xlink:type="arc" order="11"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OtherComprehensiveIncomeLossNetOfTaxPortionAttributableToParent_9f94a8d5-05b1-4090-8f27-b48a7127a059" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_OtherComprehensiveIncomeLossNetOfTaxPortionAttributableToParent"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_2da2f3e5-63d9-4ce8-9960-53f87f4b86e4" xlink:to="loc_us-gaap_OtherComprehensiveIncomeLossNetOfTaxPortionAttributableToParent_9f94a8d5-05b1-4090-8f27-b48a7127a059" xlink:type="arc" order="12"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_NetIncomeLoss_69a98e5a-791e-4a5a-849c-26c728aec631" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_NetIncomeLoss"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_2da2f3e5-63d9-4ce8-9960-53f87f4b86e4" xlink:to="loc_us-gaap_NetIncomeLoss_69a98e5a-791e-4a5a-849c-26c728aec631" xlink:type="arc" order="13"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SharesOutstanding_22c569f3-95bd-49f6-833c-93c319db1472" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_SharesOutstanding"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StockholdersEquity_c2bfe69d-972e-459c-904c-b0ebb7f77aea" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_StockholdersEquity"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.esperion.com/role/TheCompanyandBasisofPresentationDetails" xlink:type="simple" xlink:href="espr-20240331.xsd#TheCompanyandBasisofPresentationDetails"/>
  <link:definitionLink xlink:role="http://www.esperion.com/role/TheCompanyandBasisofPresentationDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_e580f5fa-ed05-4fb6-8760-b0c770888a4d" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable_6aeb91fb-89f2-4727-9514-7429434fa996" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_e580f5fa-ed05-4fb6-8760-b0c770888a4d" xlink:to="loc_us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable_6aeb91fb-89f2-4727-9514-7429434fa996" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RangeAxis_828a5632-66cb-4679-8f69-974cf9191348" xlink:href="https://xbrl.fasb.org/srt/2023/elts/srt-2023.xsd#srt_RangeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable_6aeb91fb-89f2-4727-9514-7429434fa996" xlink:to="loc_srt_RangeAxis_828a5632-66cb-4679-8f69-974cf9191348" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RangeMember_828a5632-66cb-4679-8f69-974cf9191348_default" xlink:href="https://xbrl.fasb.org/srt/2023/elts/srt-2023.xsd#srt_RangeMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_RangeAxis_828a5632-66cb-4679-8f69-974cf9191348" xlink:to="loc_srt_RangeMember_828a5632-66cb-4679-8f69-974cf9191348_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RangeMember_b2cd4ac4-2c0f-4574-a989-c59092336820" xlink:href="https://xbrl.fasb.org/srt/2023/elts/srt-2023.xsd#srt_RangeMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_RangeAxis_828a5632-66cb-4679-8f69-974cf9191348" xlink:to="loc_srt_RangeMember_b2cd4ac4-2c0f-4574-a989-c59092336820" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_MinimumMember_55af497f-4760-47e1-b780-17f77cdaecb9" xlink:href="https://xbrl.fasb.org/srt/2023/elts/srt-2023.xsd#srt_MinimumMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_RangeMember_b2cd4ac4-2c0f-4574-a989-c59092336820" xlink:to="loc_srt_MinimumMember_55af497f-4760-47e1-b780-17f77cdaecb9" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SubsidiarySaleOfStockAxis_d11a2afc-3a1b-4661-a27f-562444ae4006" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_SubsidiarySaleOfStockAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable_6aeb91fb-89f2-4727-9514-7429434fa996" xlink:to="loc_us-gaap_SubsidiarySaleOfStockAxis_d11a2afc-3a1b-4661-a27f-562444ae4006" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SaleOfStockNameOfTransactionDomain_d11a2afc-3a1b-4661-a27f-562444ae4006_default" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_SaleOfStockNameOfTransactionDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_SubsidiarySaleOfStockAxis_d11a2afc-3a1b-4661-a27f-562444ae4006" xlink:to="loc_us-gaap_SaleOfStockNameOfTransactionDomain_d11a2afc-3a1b-4661-a27f-562444ae4006_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SaleOfStockNameOfTransactionDomain_e22679f0-d0f3-482d-bab7-a83dfe8b0ac3" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_SaleOfStockNameOfTransactionDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_SubsidiarySaleOfStockAxis_d11a2afc-3a1b-4661-a27f-562444ae4006" xlink:to="loc_us-gaap_SaleOfStockNameOfTransactionDomain_e22679f0-d0f3-482d-bab7-a83dfe8b0ac3" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_CommitmentOfferingMember_f57173d3-b306-462e-9266-fe58fd9544c3" xlink:href="espr-20240331.xsd#espr_CommitmentOfferingMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SaleOfStockNameOfTransactionDomain_e22679f0-d0f3-482d-bab7-a83dfe8b0ac3" xlink:to="loc_espr_CommitmentOfferingMember_f57173d3-b306-462e-9266-fe58fd9544c3" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OverAllotmentOptionMember_a003e96f-b14f-4f36-90f3-60b70db0cf88" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_OverAllotmentOptionMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SaleOfStockNameOfTransactionDomain_e22679f0-d0f3-482d-bab7-a83dfe8b0ac3" xlink:to="loc_us-gaap_OverAllotmentOptionMember_a003e96f-b14f-4f36-90f3-60b70db0cf88" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_NumberOfProductsApproved_898eef18-3b70-4de0-ab02-ecc574f21967" xlink:href="espr-20240331.xsd#espr_NumberOfProductsApproved"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_e580f5fa-ed05-4fb6-8760-b0c770888a4d" xlink:to="loc_espr_NumberOfProductsApproved_898eef18-3b70-4de0-ab02-ecc574f21967" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_EstimatedNumberOfStudyPatients_7680b656-e06f-4a3e-91b1-8808a53c9fa9" xlink:href="espr-20240331.xsd#espr_EstimatedNumberOfStudyPatients"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_e580f5fa-ed05-4fb6-8760-b0c770888a4d" xlink:to="loc_espr_EstimatedNumberOfStudyPatients_7680b656-e06f-4a3e-91b1-8808a53c9fa9" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_SettlementAgreementAggregatePaymentFromPartner_91c21c2c-39c4-4d38-b1c0-ad2bfb31db7e" xlink:href="espr-20240331.xsd#espr_SettlementAgreementAggregatePaymentFromPartner"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_e580f5fa-ed05-4fb6-8760-b0c770888a4d" xlink:to="loc_espr_SettlementAgreementAggregatePaymentFromPartner_91c21c2c-39c4-4d38-b1c0-ad2bfb31db7e" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_SettlementAgreementAggregateFirstMilestonePaymentFromPartner_99dde615-e675-4622-ab48-cd4de70ecf04" xlink:href="espr-20240331.xsd#espr_SettlementAgreementAggregateFirstMilestonePaymentFromPartner"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_e580f5fa-ed05-4fb6-8760-b0c770888a4d" xlink:to="loc_espr_SettlementAgreementAggregateFirstMilestonePaymentFromPartner_99dde615-e675-4622-ab48-cd4de70ecf04" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_SettlementAgreementTimeRequiredToPayCashPortionOfSettlement_a1a64eb6-b410-4370-85c3-9241dc7b2e7b" xlink:href="espr-20240331.xsd#espr_SettlementAgreementTimeRequiredToPayCashPortionOfSettlement"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_e580f5fa-ed05-4fb6-8760-b0c770888a4d" xlink:to="loc_espr_SettlementAgreementTimeRequiredToPayCashPortionOfSettlement_a1a64eb6-b410-4370-85c3-9241dc7b2e7b" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_SettlementAgreementAggregateSecondMilestonePaymentFromPartner_db852441-c141-4cec-942f-a82487f2ba3a" xlink:href="espr-20240331.xsd#espr_SettlementAgreementAggregateSecondMilestonePaymentFromPartner"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_e580f5fa-ed05-4fb6-8760-b0c770888a4d" xlink:to="loc_espr_SettlementAgreementAggregateSecondMilestonePaymentFromPartner_db852441-c141-4cec-942f-a82487f2ba3a" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SaleOfStockNumberOfSharesIssuedInTransaction_465618f4-d89a-4e04-a8fd-171b43fbbffc" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_SaleOfStockNumberOfSharesIssuedInTransaction"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_e580f5fa-ed05-4fb6-8760-b0c770888a4d" xlink:to="loc_us-gaap_SaleOfStockNumberOfSharesIssuedInTransaction_465618f4-d89a-4e04-a8fd-171b43fbbffc" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SaleOfStockPricePerShare_13210504-0d9e-4a0d-8b84-989c0839f418" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_SaleOfStockPricePerShare"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_e580f5fa-ed05-4fb6-8760-b0c770888a4d" xlink:to="loc_us-gaap_SaleOfStockPricePerShare_13210504-0d9e-4a0d-8b84-989c0839f418" xlink:type="arc" order="7"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_SaleOfStockUnderwriterOptionPeriod_ec0954b8-22e8-495e-83ce-f5e6ffc17f77" xlink:href="espr-20240331.xsd#espr_SaleOfStockUnderwriterOptionPeriod"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_e580f5fa-ed05-4fb6-8760-b0c770888a4d" xlink:to="loc_espr_SaleOfStockUnderwriterOptionPeriod_ec0954b8-22e8-495e-83ce-f5e6ffc17f77" xlink:type="arc" order="8"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SaleOfStockConsiderationReceivedOnTransaction_09ca3c65-39fa-4528-abdd-e287084310e4" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_SaleOfStockConsiderationReceivedOnTransaction"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_e580f5fa-ed05-4fb6-8760-b0c770888a4d" xlink:to="loc_us-gaap_SaleOfStockConsiderationReceivedOnTransaction_09ca3c65-39fa-4528-abdd-e287084310e4" xlink:type="arc" order="9"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PaymentsForCommissions_1cb8d841-dd1f-4c70-ac37-8a9f2b0cef81" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_PaymentsForCommissions"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_e580f5fa-ed05-4fb6-8760-b0c770888a4d" xlink:to="loc_us-gaap_PaymentsForCommissions_1cb8d841-dd1f-4c70-ac37-8a9f2b0cef81" xlink:type="arc" order="10"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.esperion.com/role/SummaryofSignificantAccountingPoliciesDetails" xlink:type="simple" xlink:href="espr-20240331.xsd#SummaryofSignificantAccountingPoliciesDetails"/>
  <link:definitionLink xlink:role="http://www.esperion.com/role/SummaryofSignificantAccountingPoliciesDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_espr_SignificantAccountingPoliciesLineItems_9b2eac79-61e7-492f-abbd-b88e592cee2d" xlink:href="espr-20240331.xsd#espr_SignificantAccountingPoliciesLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_SignificantAccountingPoliciesTable_2b965ba1-f5bc-4c0f-9d6c-7b0ddd5fb540" xlink:href="espr-20240331.xsd#espr_SignificantAccountingPoliciesTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_espr_SignificantAccountingPoliciesLineItems_9b2eac79-61e7-492f-abbd-b88e592cee2d" xlink:to="loc_espr_SignificantAccountingPoliciesTable_2b965ba1-f5bc-4c0f-9d6c-7b0ddd5fb540" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ConcentrationRiskByBenchmarkAxis_cce8dc06-1f5e-43ee-902d-3bac37f5f986" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ConcentrationRiskByBenchmarkAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_espr_SignificantAccountingPoliciesTable_2b965ba1-f5bc-4c0f-9d6c-7b0ddd5fb540" xlink:to="loc_us-gaap_ConcentrationRiskByBenchmarkAxis_cce8dc06-1f5e-43ee-902d-3bac37f5f986" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ConcentrationRiskBenchmarkDomain_cce8dc06-1f5e-43ee-902d-3bac37f5f986_default" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ConcentrationRiskBenchmarkDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_ConcentrationRiskByBenchmarkAxis_cce8dc06-1f5e-43ee-902d-3bac37f5f986" xlink:to="loc_us-gaap_ConcentrationRiskBenchmarkDomain_cce8dc06-1f5e-43ee-902d-3bac37f5f986_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ConcentrationRiskBenchmarkDomain_bed2e485-5bbe-4b91-9b35-7b7137c5f2d8" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ConcentrationRiskBenchmarkDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_ConcentrationRiskByBenchmarkAxis_cce8dc06-1f5e-43ee-902d-3bac37f5f986" xlink:to="loc_us-gaap_ConcentrationRiskBenchmarkDomain_bed2e485-5bbe-4b91-9b35-7b7137c5f2d8" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_TradeAccountsReceivableMember_562baa61-e8ec-46e7-89a3-4c2616bbb850" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_TradeAccountsReceivableMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ConcentrationRiskBenchmarkDomain_bed2e485-5bbe-4b91-9b35-7b7137c5f2d8" xlink:to="loc_us-gaap_TradeAccountsReceivableMember_562baa61-e8ec-46e7-89a3-4c2616bbb850" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SalesRevenueNetMember_4dd94c84-3e95-4677-81e0-4724ecd34c7e" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_SalesRevenueNetMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ConcentrationRiskBenchmarkDomain_bed2e485-5bbe-4b91-9b35-7b7137c5f2d8" xlink:to="loc_us-gaap_SalesRevenueNetMember_4dd94c84-3e95-4677-81e0-4724ecd34c7e" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ConcentrationRiskByTypeAxis_257a4859-c430-426c-b2da-d39b64ec5f3b" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ConcentrationRiskByTypeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_espr_SignificantAccountingPoliciesTable_2b965ba1-f5bc-4c0f-9d6c-7b0ddd5fb540" xlink:to="loc_us-gaap_ConcentrationRiskByTypeAxis_257a4859-c430-426c-b2da-d39b64ec5f3b" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ConcentrationRiskTypeDomain_257a4859-c430-426c-b2da-d39b64ec5f3b_default" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ConcentrationRiskTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_ConcentrationRiskByTypeAxis_257a4859-c430-426c-b2da-d39b64ec5f3b" xlink:to="loc_us-gaap_ConcentrationRiskTypeDomain_257a4859-c430-426c-b2da-d39b64ec5f3b_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ConcentrationRiskTypeDomain_d1da7eef-98c0-4fe3-a16f-394448145fed" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ConcentrationRiskTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_ConcentrationRiskByTypeAxis_257a4859-c430-426c-b2da-d39b64ec5f3b" xlink:to="loc_us-gaap_ConcentrationRiskTypeDomain_d1da7eef-98c0-4fe3-a16f-394448145fed" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CustomerConcentrationRiskMember_a9a8ef49-4480-44a1-9cf1-d39880c14d25" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_CustomerConcentrationRiskMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ConcentrationRiskTypeDomain_d1da7eef-98c0-4fe3-a16f-394448145fed" xlink:to="loc_us-gaap_CustomerConcentrationRiskMember_a9a8ef49-4480-44a1-9cf1-d39880c14d25" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_AccountsReceivableRisksMember_6e3a3b22-ea33-4c58-814a-14c6773c91d3" xlink:href="espr-20240331.xsd#espr_AccountsReceivableRisksMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ConcentrationRiskTypeDomain_d1da7eef-98c0-4fe3-a16f-394448145fed" xlink:to="loc_espr_AccountsReceivableRisksMember_6e3a3b22-ea33-4c58-814a-14c6773c91d3" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ProductConcentrationRiskMember_7942a621-e58b-4e12-9ef6-1c21e7d160dc" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ProductConcentrationRiskMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ConcentrationRiskTypeDomain_d1da7eef-98c0-4fe3-a16f-394448145fed" xlink:to="loc_us-gaap_ProductConcentrationRiskMember_7942a621-e58b-4e12-9ef6-1c21e7d160dc" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductOrServiceAxis_20b68110-a16c-4106-896c-db9372f9afa8" xlink:href="https://xbrl.fasb.org/srt/2023/elts/srt-2023.xsd#srt_ProductOrServiceAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_espr_SignificantAccountingPoliciesTable_2b965ba1-f5bc-4c0f-9d6c-7b0ddd5fb540" xlink:to="loc_srt_ProductOrServiceAxis_20b68110-a16c-4106-896c-db9372f9afa8" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductsAndServicesDomain_20b68110-a16c-4106-896c-db9372f9afa8_default" xlink:href="https://xbrl.fasb.org/srt/2023/elts/srt-2023.xsd#srt_ProductsAndServicesDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_ProductOrServiceAxis_20b68110-a16c-4106-896c-db9372f9afa8" xlink:to="loc_srt_ProductsAndServicesDomain_20b68110-a16c-4106-896c-db9372f9afa8_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductsAndServicesDomain_7cc9dae0-d42b-4425-bcf9-1a9c82244730" xlink:href="https://xbrl.fasb.org/srt/2023/elts/srt-2023.xsd#srt_ProductsAndServicesDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_ProductOrServiceAxis_20b68110-a16c-4106-896c-db9372f9afa8" xlink:to="loc_srt_ProductsAndServicesDomain_7cc9dae0-d42b-4425-bcf9-1a9c82244730" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ProductMember_9a13b3c0-68f9-42de-8c55-21ecb62af073" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ProductMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ProductsAndServicesDomain_7cc9dae0-d42b-4425-bcf9-1a9c82244730" xlink:to="loc_us-gaap_ProductMember_9a13b3c0-68f9-42de-8c55-21ecb62af073" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_MajorCustomersAxis_4e5ccd67-c0d8-4114-af14-ac653bcbe183" xlink:href="https://xbrl.fasb.org/srt/2023/elts/srt-2023.xsd#srt_MajorCustomersAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_espr_SignificantAccountingPoliciesTable_2b965ba1-f5bc-4c0f-9d6c-7b0ddd5fb540" xlink:to="loc_srt_MajorCustomersAxis_4e5ccd67-c0d8-4114-af14-ac653bcbe183" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_NameOfMajorCustomerDomain_4e5ccd67-c0d8-4114-af14-ac653bcbe183_default" xlink:href="https://xbrl.fasb.org/srt/2023/elts/srt-2023.xsd#srt_NameOfMajorCustomerDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_MajorCustomersAxis_4e5ccd67-c0d8-4114-af14-ac653bcbe183" xlink:to="loc_srt_NameOfMajorCustomerDomain_4e5ccd67-c0d8-4114-af14-ac653bcbe183_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_NameOfMajorCustomerDomain_bfa6782f-e646-43de-b141-c84a39a415da" xlink:href="https://xbrl.fasb.org/srt/2023/elts/srt-2023.xsd#srt_NameOfMajorCustomerDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_MajorCustomersAxis_4e5ccd67-c0d8-4114-af14-ac653bcbe183" xlink:to="loc_srt_NameOfMajorCustomerDomain_bfa6782f-e646-43de-b141-c84a39a415da" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_ThreeLargestCustomersMember_d903de5c-25e8-4953-be11-11b279daafaf" xlink:href="espr-20240331.xsd#espr_ThreeLargestCustomersMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_NameOfMajorCustomerDomain_bfa6782f-e646-43de-b141-c84a39a415da" xlink:to="loc_espr_ThreeLargestCustomersMember_d903de5c-25e8-4953-be11-11b279daafaf" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_ConcentrationRiskNumberOfMajorCustomers_8e5f0d0d-fb83-476b-b22b-eb5917a407c8" xlink:href="espr-20240331.xsd#espr_ConcentrationRiskNumberOfMajorCustomers"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_espr_SignificantAccountingPoliciesLineItems_9b2eac79-61e7-492f-abbd-b88e592cee2d" xlink:to="loc_espr_ConcentrationRiskNumberOfMajorCustomers_8e5f0d0d-fb83-476b-b22b-eb5917a407c8" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ConcentrationRiskPercentage1_d6279bf2-4f01-4d96-be81-f666c553f861" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ConcentrationRiskPercentage1"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_espr_SignificantAccountingPoliciesLineItems_9b2eac79-61e7-492f-abbd-b88e592cee2d" xlink:to="loc_us-gaap_ConcentrationRiskPercentage1_d6279bf2-4f01-4d96-be81-f666c553f861" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_NumberOfSourcesOfRevenue_9a7e14f7-9e23-47d5-bd66-b6f3f27f0da6" xlink:href="espr-20240331.xsd#espr_NumberOfSourcesOfRevenue"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_espr_SignificantAccountingPoliciesLineItems_9b2eac79-61e7-492f-abbd-b88e592cee2d" xlink:to="loc_espr_NumberOfSourcesOfRevenue_9a7e14f7-9e23-47d5-bd66-b6f3f27f0da6" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax_3ba976f5-9e38-4497-a167-8b1cf6682ca5" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_espr_SignificantAccountingPoliciesLineItems_9b2eac79-61e7-492f-abbd-b88e592cee2d" xlink:to="loc_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax_3ba976f5-9e38-4497-a167-8b1cf6682ca5" xlink:type="arc" order="3"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.esperion.com/role/CollaborationswithThirdPartiesDetails" xlink:type="simple" xlink:href="espr-20240331.xsd#CollaborationswithThirdPartiesDetails"/>
  <link:definitionLink xlink:role="http://www.esperion.com/role/CollaborationswithThirdPartiesDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_d2b8e88b-a3fd-4154-9ac0-d4f5a8253d7f" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable_ce5e0c95-3afb-4a77-9a47-10e165bc974d" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_d2b8e88b-a3fd-4154-9ac0-d4f5a8253d7f" xlink:to="loc_us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable_ce5e0c95-3afb-4a77-9a47-10e165bc974d" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_CounterpartyNameAxis_0928dfdc-d5d8-436d-9a33-3234610f9c65" xlink:href="https://xbrl.fasb.org/srt/2023/elts/srt-2023.xsd#srt_CounterpartyNameAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable_ce5e0c95-3afb-4a77-9a47-10e165bc974d" xlink:to="loc_srt_CounterpartyNameAxis_0928dfdc-d5d8-436d-9a33-3234610f9c65" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RepurchaseAgreementCounterpartyNameDomain_0928dfdc-d5d8-436d-9a33-3234610f9c65_default" xlink:href="https://xbrl.fasb.org/srt/2023/elts/srt-2023.xsd#srt_RepurchaseAgreementCounterpartyNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_CounterpartyNameAxis_0928dfdc-d5d8-436d-9a33-3234610f9c65" xlink:to="loc_srt_RepurchaseAgreementCounterpartyNameDomain_0928dfdc-d5d8-436d-9a33-3234610f9c65_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RepurchaseAgreementCounterpartyNameDomain_a879048f-bdf2-4143-a05d-7ed4a04118d7" xlink:href="https://xbrl.fasb.org/srt/2023/elts/srt-2023.xsd#srt_RepurchaseAgreementCounterpartyNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_CounterpartyNameAxis_0928dfdc-d5d8-436d-9a33-3234610f9c65" xlink:to="loc_srt_RepurchaseAgreementCounterpartyNameDomain_a879048f-bdf2-4143-a05d-7ed4a04118d7" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_DaiichiSankyoEuropeGmbhMember_5a05172b-cb8e-40ef-ad7b-45107da20d71" xlink:href="espr-20240331.xsd#espr_DaiichiSankyoEuropeGmbhMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_RepurchaseAgreementCounterpartyNameDomain_a879048f-bdf2-4143-a05d-7ed4a04118d7" xlink:to="loc_espr_DaiichiSankyoEuropeGmbhMember_5a05172b-cb8e-40ef-ad7b-45107da20d71" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_OtsukaPharmaceuticalCoLtdMember_16c0f86e-5dcb-4cd5-8bc2-9ff267ad085d" xlink:href="espr-20240331.xsd#espr_OtsukaPharmaceuticalCoLtdMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_RepurchaseAgreementCounterpartyNameDomain_a879048f-bdf2-4143-a05d-7ed4a04118d7" xlink:to="loc_espr_OtsukaPharmaceuticalCoLtdMember_16c0f86e-5dcb-4cd5-8bc2-9ff267ad085d" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_DaiichiSankyoCoLtdMember_1fb775f3-4866-44f6-b3a6-f9cc2de9d8b1" xlink:href="espr-20240331.xsd#espr_DaiichiSankyoCoLtdMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_RepurchaseAgreementCounterpartyNameDomain_a879048f-bdf2-4143-a05d-7ed4a04118d7" xlink:to="loc_espr_DaiichiSankyoCoLtdMember_1fb775f3-4866-44f6-b3a6-f9cc2de9d8b1" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_TypeOfArrangementAxis_59a5408c-a5aa-4193-a285-7d2458a97382" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_TypeOfArrangementAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable_ce5e0c95-3afb-4a77-9a47-10e165bc974d" xlink:to="loc_us-gaap_TypeOfArrangementAxis_59a5408c-a5aa-4193-a285-7d2458a97382" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ArrangementsAndNonarrangementTransactionsMember_59a5408c-a5aa-4193-a285-7d2458a97382_default" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ArrangementsAndNonarrangementTransactionsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_TypeOfArrangementAxis_59a5408c-a5aa-4193-a285-7d2458a97382" xlink:to="loc_us-gaap_ArrangementsAndNonarrangementTransactionsMember_59a5408c-a5aa-4193-a285-7d2458a97382_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ArrangementsAndNonarrangementTransactionsMember_d9428d8e-941a-408e-80ed-07887d2f14db" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ArrangementsAndNonarrangementTransactionsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_TypeOfArrangementAxis_59a5408c-a5aa-4193-a285-7d2458a97382" xlink:to="loc_us-gaap_ArrangementsAndNonarrangementTransactionsMember_d9428d8e-941a-408e-80ed-07887d2f14db" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CollaborativeArrangementMember_d2a7a505-4b43-4a69-a238-f96ab67cff3d" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_CollaborativeArrangementMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ArrangementsAndNonarrangementTransactionsMember_d9428d8e-941a-408e-80ed-07887d2f14db" xlink:to="loc_us-gaap_CollaborativeArrangementMember_d2a7a505-4b43-4a69-a238-f96ab67cff3d" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_ExclusiveDevelopmentalActivitiesMember_4e6fdac7-ea1a-4610-90a3-0a3eb57f4b63" xlink:href="espr-20240331.xsd#espr_ExclusiveDevelopmentalActivitiesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ArrangementsAndNonarrangementTransactionsMember_d9428d8e-941a-408e-80ed-07887d2f14db" xlink:to="loc_espr_ExclusiveDevelopmentalActivitiesMember_4e6fdac7-ea1a-4610-90a3-0a3eb57f4b63" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RangeAxis_902b5669-a45e-47b0-8f22-0946bdfa2b81" xlink:href="https://xbrl.fasb.org/srt/2023/elts/srt-2023.xsd#srt_RangeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable_ce5e0c95-3afb-4a77-9a47-10e165bc974d" xlink:to="loc_srt_RangeAxis_902b5669-a45e-47b0-8f22-0946bdfa2b81" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RangeMember_902b5669-a45e-47b0-8f22-0946bdfa2b81_default" xlink:href="https://xbrl.fasb.org/srt/2023/elts/srt-2023.xsd#srt_RangeMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_RangeAxis_902b5669-a45e-47b0-8f22-0946bdfa2b81" xlink:to="loc_srt_RangeMember_902b5669-a45e-47b0-8f22-0946bdfa2b81_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RangeMember_371388fa-ecd6-4051-b96e-11140f022e1e" xlink:href="https://xbrl.fasb.org/srt/2023/elts/srt-2023.xsd#srt_RangeMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_RangeAxis_902b5669-a45e-47b0-8f22-0946bdfa2b81" xlink:to="loc_srt_RangeMember_371388fa-ecd6-4051-b96e-11140f022e1e" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_MinimumMember_2cadfe80-2f4c-41f0-bab9-5cca3e6a58ed" xlink:href="https://xbrl.fasb.org/srt/2023/elts/srt-2023.xsd#srt_MinimumMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_RangeMember_371388fa-ecd6-4051-b96e-11140f022e1e" xlink:to="loc_srt_MinimumMember_2cadfe80-2f4c-41f0-bab9-5cca3e6a58ed" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_MaximumMember_1417fc96-8eed-4a21-a217-7e4a8d8f016b" xlink:href="https://xbrl.fasb.org/srt/2023/elts/srt-2023.xsd#srt_MaximumMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_RangeMember_371388fa-ecd6-4051-b96e-11140f022e1e" xlink:to="loc_srt_MaximumMember_1417fc96-8eed-4a21-a217-7e4a8d8f016b" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductOrServiceAxis_b4d25a01-7b14-450c-809d-96015034be10" xlink:href="https://xbrl.fasb.org/srt/2023/elts/srt-2023.xsd#srt_ProductOrServiceAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable_ce5e0c95-3afb-4a77-9a47-10e165bc974d" xlink:to="loc_srt_ProductOrServiceAxis_b4d25a01-7b14-450c-809d-96015034be10" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductsAndServicesDomain_b4d25a01-7b14-450c-809d-96015034be10_default" xlink:href="https://xbrl.fasb.org/srt/2023/elts/srt-2023.xsd#srt_ProductsAndServicesDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_ProductOrServiceAxis_b4d25a01-7b14-450c-809d-96015034be10" xlink:to="loc_srt_ProductsAndServicesDomain_b4d25a01-7b14-450c-809d-96015034be10_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductsAndServicesDomain_6987b5f6-0ec0-4bad-98c8-13d7fea3a79b" xlink:href="https://xbrl.fasb.org/srt/2023/elts/srt-2023.xsd#srt_ProductsAndServicesDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_ProductOrServiceAxis_b4d25a01-7b14-450c-809d-96015034be10" xlink:to="loc_srt_ProductsAndServicesDomain_6987b5f6-0ec0-4bad-98c8-13d7fea3a79b" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_RoyaltyRevenueAndProductSalesBulkTabletsMember_192662aa-8cce-4582-be02-fb4b1506701c" xlink:href="espr-20240331.xsd#espr_RoyaltyRevenueAndProductSalesBulkTabletsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ProductsAndServicesDomain_6987b5f6-0ec0-4bad-98c8-13d7fea3a79b" xlink:to="loc_espr_RoyaltyRevenueAndProductSalesBulkTabletsMember_192662aa-8cce-4582-be02-fb4b1506701c" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_UpFrontPayment_0de7e960-4bd2-4faf-8b59-717e74e545d1" xlink:href="espr-20240331.xsd#espr_UpFrontPayment"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_d2b8e88b-a3fd-4154-9ac0-d4f5a8253d7f" xlink:to="loc_espr_UpFrontPayment_0de7e960-4bd2-4faf-8b59-717e74e545d1" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_CashPaymentToBeReceivedUponFirstCommercialSales_4d6a47b1-9f2b-451b-a10c-546103080ed8" xlink:href="espr-20240331.xsd#espr_CashPaymentToBeReceivedUponFirstCommercialSales"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_d2b8e88b-a3fd-4154-9ac0-d4f5a8253d7f" xlink:to="loc_espr_CashPaymentToBeReceivedUponFirstCommercialSales_4d6a47b1-9f2b-451b-a10c-546103080ed8" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_PercentageOfRoyaltiesToBeReceivedOnNetSales_4545eb45-a059-4a7b-aa26-dda7bdf7696a" xlink:href="espr-20240331.xsd#espr_PercentageOfRoyaltiesToBeReceivedOnNetSales"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_d2b8e88b-a3fd-4154-9ac0-d4f5a8253d7f" xlink:to="loc_espr_PercentageOfRoyaltiesToBeReceivedOnNetSales_4545eb45-a059-4a7b-aa26-dda7bdf7696a" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_SettlementAgreementAggregatePaymentFromPartner_00d4b0f6-ef2a-422b-a92f-07ee8d9805bb" xlink:href="espr-20240331.xsd#espr_SettlementAgreementAggregatePaymentFromPartner"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_d2b8e88b-a3fd-4154-9ac0-d4f5a8253d7f" xlink:to="loc_espr_SettlementAgreementAggregatePaymentFromPartner_00d4b0f6-ef2a-422b-a92f-07ee8d9805bb" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_SettlementAgreementAggregateFirstMilestonePaymentFromPartner_01765b44-03db-4197-bee9-83af0d9713aa" xlink:href="espr-20240331.xsd#espr_SettlementAgreementAggregateFirstMilestonePaymentFromPartner"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_d2b8e88b-a3fd-4154-9ac0-d4f5a8253d7f" xlink:to="loc_espr_SettlementAgreementAggregateFirstMilestonePaymentFromPartner_01765b44-03db-4197-bee9-83af0d9713aa" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_SettlementAgreementTimeRequiredToPayCashPortionOfSettlement_63b6a738-216a-4749-ac74-8041530a1a27" xlink:href="espr-20240331.xsd#espr_SettlementAgreementTimeRequiredToPayCashPortionOfSettlement"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_d2b8e88b-a3fd-4154-9ac0-d4f5a8253d7f" xlink:to="loc_espr_SettlementAgreementTimeRequiredToPayCashPortionOfSettlement_63b6a738-216a-4749-ac74-8041530a1a27" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_SettlementAgreementAggregateSecondMilestonePaymentFromPartner_ea39f9e8-e5fe-4322-b1f9-87bd8166e54f" xlink:href="espr-20240331.xsd#espr_SettlementAgreementAggregateSecondMilestonePaymentFromPartner"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_d2b8e88b-a3fd-4154-9ac0-d4f5a8253d7f" xlink:to="loc_espr_SettlementAgreementAggregateSecondMilestonePaymentFromPartner_ea39f9e8-e5fe-4322-b1f9-87bd8166e54f" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax_2b458882-d807-4ce6-9b76-c4092389babd" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_d2b8e88b-a3fd-4154-9ac0-d4f5a8253d7f" xlink:to="loc_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax_2b458882-d807-4ce6-9b76-c4092389babd" xlink:type="arc" order="7"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_AggregateAmountOfPotentialFutureRevenueTotalDevelopmentAndSalesMilestones_84b0db9e-eaf1-4c04-8e0a-223a462d42b3" xlink:href="espr-20240331.xsd#espr_AggregateAmountOfPotentialFutureRevenueTotalDevelopmentAndSalesMilestones"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_d2b8e88b-a3fd-4154-9ac0-d4f5a8253d7f" xlink:to="loc_espr_AggregateAmountOfPotentialFutureRevenueTotalDevelopmentAndSalesMilestones_84b0db9e-eaf1-4c04-8e0a-223a462d42b3" xlink:type="arc" order="8"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_FuturePaymentMilestoneFirstSubmissionOfJapaneseNewDrugApplicationOtsukaTerritory_9249a026-fca7-45a4-9072-2de8f0e1234f" xlink:href="espr-20240331.xsd#espr_FuturePaymentMilestoneFirstSubmissionOfJapaneseNewDrugApplicationOtsukaTerritory"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_d2b8e88b-a3fd-4154-9ac0-d4f5a8253d7f" xlink:to="loc_espr_FuturePaymentMilestoneFirstSubmissionOfJapaneseNewDrugApplicationOtsukaTerritory_9249a026-fca7-45a4-9072-2de8f0e1234f" xlink:type="arc" order="9"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_FuturePaymentMilestoneFirstNationalHealthInsurancePriceListingOtsukaTerritory_edd1bfdc-19e7-47d6-8f6a-3547f914cad0" xlink:href="espr-20240331.xsd#espr_FuturePaymentMilestoneFirstNationalHealthInsurancePriceListingOtsukaTerritory"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_d2b8e88b-a3fd-4154-9ac0-d4f5a8253d7f" xlink:to="loc_espr_FuturePaymentMilestoneFirstNationalHealthInsurancePriceListingOtsukaTerritory_edd1bfdc-19e7-47d6-8f6a-3547f914cad0" xlink:type="arc" order="10"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_FuturePaymentMilestoneAchievementOfDrugTrialOutcomesStudies_df3c80a1-54a5-487f-b6ed-df0e14c077c3" xlink:href="espr-20240331.xsd#espr_FuturePaymentMilestoneAchievementOfDrugTrialOutcomesStudies"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_d2b8e88b-a3fd-4154-9ac0-d4f5a8253d7f" xlink:to="loc_espr_FuturePaymentMilestoneAchievementOfDrugTrialOutcomesStudies_df3c80a1-54a5-487f-b6ed-df0e14c077c3" xlink:type="arc" order="11"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_FuturePaymentMilestoneSalesMilestones_97b90c64-8830-44d5-ab93-6b6983e77de1" xlink:href="espr-20240331.xsd#espr_FuturePaymentMilestoneSalesMilestones"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_d2b8e88b-a3fd-4154-9ac0-d4f5a8253d7f" xlink:to="loc_espr_FuturePaymentMilestoneSalesMilestones_97b90c64-8830-44d5-ab93-6b6983e77de1" xlink:type="arc" order="12"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_FutureUpFrontPayment_2877eaab-227e-4036-aae4-f9fca902ad3d" xlink:href="espr-20240331.xsd#espr_FutureUpFrontPayment"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_d2b8e88b-a3fd-4154-9ac0-d4f5a8253d7f" xlink:to="loc_espr_FutureUpFrontPayment_2877eaab-227e-4036-aae4-f9fca902ad3d" xlink:type="arc" order="13"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_CashPaymentToBeReceivedUponCertainCommercialMilestones_6f071a05-a01b-4a01-8448-caa85c3258ef" xlink:href="espr-20240331.xsd#espr_CashPaymentToBeReceivedUponCertainCommercialMilestones"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_d2b8e88b-a3fd-4154-9ac0-d4f5a8253d7f" xlink:to="loc_espr_CashPaymentToBeReceivedUponCertainCommercialMilestones_6f071a05-a01b-4a01-8448-caa85c3258ef" xlink:type="arc" order="14"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.esperion.com/role/CommitmentsandContingenciesDetails" xlink:type="simple" xlink:href="espr-20240331.xsd#CommitmentsandContingenciesDetails"/>
  <link:definitionLink xlink:role="http://www.esperion.com/role/CommitmentsandContingenciesDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LossContingenciesLineItems_58581231-c52b-484b-b3aa-d826397e334a" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_LossContingenciesLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LossContingenciesTable_f64b9c08-3656-462e-bc72-fd28c401a56b" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_LossContingenciesTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_LossContingenciesLineItems_58581231-c52b-484b-b3aa-d826397e334a" xlink:to="loc_us-gaap_LossContingenciesTable_f64b9c08-3656-462e-bc72-fd28c401a56b" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_TypeOfRiskAxis_4d0ae51f-4e52-4860-9dd3-27a6c48b25e6" xlink:href="espr-20240331.xsd#espr_TypeOfRiskAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_LossContingenciesTable_f64b9c08-3656-462e-bc72-fd28c401a56b" xlink:to="loc_espr_TypeOfRiskAxis_4d0ae51f-4e52-4860-9dd3-27a6c48b25e6" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_TypeOfRiskDomain_4d0ae51f-4e52-4860-9dd3-27a6c48b25e6_default" xlink:href="espr-20240331.xsd#espr_TypeOfRiskDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_espr_TypeOfRiskAxis_4d0ae51f-4e52-4860-9dd3-27a6c48b25e6" xlink:to="loc_espr_TypeOfRiskDomain_4d0ae51f-4e52-4860-9dd3-27a6c48b25e6_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_TypeOfRiskDomain_260afb6b-002b-4e9c-86ca-edc7bae0949e" xlink:href="espr-20240331.xsd#espr_TypeOfRiskDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_espr_TypeOfRiskAxis_4d0ae51f-4e52-4860-9dd3-27a6c48b25e6" xlink:to="loc_espr_TypeOfRiskDomain_260afb6b-002b-4e9c-86ca-edc7bae0949e" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_CardiovascularRiskOutcomeGreaterThanFifteenButLessThanTwentyPercentMember_6550396d-7eb6-46f3-b804-ea29f6b9ebd0" xlink:href="espr-20240331.xsd#espr_CardiovascularRiskOutcomeGreaterThanFifteenButLessThanTwentyPercentMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_espr_TypeOfRiskDomain_260afb6b-002b-4e9c-86ca-edc7bae0949e" xlink:to="loc_espr_CardiovascularRiskOutcomeGreaterThanFifteenButLessThanTwentyPercentMember_6550396d-7eb6-46f3-b804-ea29f6b9ebd0" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_CardiovascularRiskMember_a86baf2f-1974-4888-a1c9-7c3569b864e9" xlink:href="espr-20240331.xsd#espr_CardiovascularRiskMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_espr_TypeOfRiskDomain_260afb6b-002b-4e9c-86ca-edc7bae0949e" xlink:to="loc_espr_CardiovascularRiskMember_a86baf2f-1974-4888-a1c9-7c3569b864e9" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RangeAxis_8fc7d4ae-0527-4bf6-9abf-27e552b8557d" xlink:href="https://xbrl.fasb.org/srt/2023/elts/srt-2023.xsd#srt_RangeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_LossContingenciesTable_f64b9c08-3656-462e-bc72-fd28c401a56b" xlink:to="loc_srt_RangeAxis_8fc7d4ae-0527-4bf6-9abf-27e552b8557d" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RangeMember_8fc7d4ae-0527-4bf6-9abf-27e552b8557d_default" xlink:href="https://xbrl.fasb.org/srt/2023/elts/srt-2023.xsd#srt_RangeMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_RangeAxis_8fc7d4ae-0527-4bf6-9abf-27e552b8557d" xlink:to="loc_srt_RangeMember_8fc7d4ae-0527-4bf6-9abf-27e552b8557d_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RangeMember_fee2fdaa-8d7b-46ba-9b5c-78951dea31f7" xlink:href="https://xbrl.fasb.org/srt/2023/elts/srt-2023.xsd#srt_RangeMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_RangeAxis_8fc7d4ae-0527-4bf6-9abf-27e552b8557d" xlink:to="loc_srt_RangeMember_fee2fdaa-8d7b-46ba-9b5c-78951dea31f7" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_MinimumMember_0c185845-9807-448c-a711-6121bdc2d17b" xlink:href="https://xbrl.fasb.org/srt/2023/elts/srt-2023.xsd#srt_MinimumMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_RangeMember_fee2fdaa-8d7b-46ba-9b5c-78951dea31f7" xlink:to="loc_srt_MinimumMember_0c185845-9807-448c-a711-6121bdc2d17b" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_PotentialProceedsFromPartnerMilestonePayments_d32e9a92-f1a6-4132-ad93-f14214b318f8" xlink:href="espr-20240331.xsd#espr_PotentialProceedsFromPartnerMilestonePayments"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LossContingenciesLineItems_58581231-c52b-484b-b3aa-d826397e334a" xlink:to="loc_espr_PotentialProceedsFromPartnerMilestonePayments_d32e9a92-f1a6-4132-ad93-f14214b318f8" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_PercentageOfRiskReduction_e88252f4-b5c9-45a8-b666-edf78b3f40fa" xlink:href="espr-20240331.xsd#espr_PercentageOfRiskReduction"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LossContingenciesLineItems_58581231-c52b-484b-b3aa-d826397e334a" xlink:to="loc_espr_PercentageOfRiskReduction_e88252f4-b5c9-45a8-b666-edf78b3f40fa" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_SettlementAgreementAggregatePaymentFromPartner_0deaf598-952e-4bd1-9826-36b89bf3aa37" xlink:href="espr-20240331.xsd#espr_SettlementAgreementAggregatePaymentFromPartner"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LossContingenciesLineItems_58581231-c52b-484b-b3aa-d826397e334a" xlink:to="loc_espr_SettlementAgreementAggregatePaymentFromPartner_0deaf598-952e-4bd1-9826-36b89bf3aa37" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_SettlementAgreementAggregateFirstMilestonePaymentFromPartner_3902be3c-6546-479a-aebf-e945f3028a45" xlink:href="espr-20240331.xsd#espr_SettlementAgreementAggregateFirstMilestonePaymentFromPartner"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LossContingenciesLineItems_58581231-c52b-484b-b3aa-d826397e334a" xlink:to="loc_espr_SettlementAgreementAggregateFirstMilestonePaymentFromPartner_3902be3c-6546-479a-aebf-e945f3028a45" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_SettlementAgreementTimeRequiredToPayCashPortionOfSettlement_1091c248-beee-4b03-95b9-aeecb7f49c55" xlink:href="espr-20240331.xsd#espr_SettlementAgreementTimeRequiredToPayCashPortionOfSettlement"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LossContingenciesLineItems_58581231-c52b-484b-b3aa-d826397e334a" xlink:to="loc_espr_SettlementAgreementTimeRequiredToPayCashPortionOfSettlement_1091c248-beee-4b03-95b9-aeecb7f49c55" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_SettlementAgreementAggregateSecondMilestonePaymentFromPartner_b436b2dd-0e13-4338-a7c3-1f0d704827f4" xlink:href="espr-20240331.xsd#espr_SettlementAgreementAggregateSecondMilestonePaymentFromPartner"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LossContingenciesLineItems_58581231-c52b-484b-b3aa-d826397e334a" xlink:to="loc_espr_SettlementAgreementAggregateSecondMilestonePaymentFromPartner_b436b2dd-0e13-4338-a7c3-1f0d704827f4" xlink:type="arc" order="5"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.esperion.com/role/InvestmentsSummaryofCashEquivalentsandShortTermInvestmentsDetails" xlink:type="simple" xlink:href="espr-20240331.xsd#InvestmentsSummaryofCashEquivalentsandShortTermInvestmentsDetails"/>
  <link:definitionLink xlink:role="http://www.esperion.com/role/InvestmentsSummaryofCashEquivalentsandShortTermInvestmentsDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfAvailableForSaleSecuritiesLineItems_20a39327-5072-42cd-a427-dd46c26e6be4" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ScheduleOfAvailableForSaleSecuritiesLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtSecuritiesAvailableForSaleTable_8500e2e6-9f2e-4028-953e-996112d28eb2" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_DebtSecuritiesAvailableForSaleTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_ScheduleOfAvailableForSaleSecuritiesLineItems_20a39327-5072-42cd-a427-dd46c26e6be4" xlink:to="loc_us-gaap_DebtSecuritiesAvailableForSaleTable_8500e2e6-9f2e-4028-953e-996112d28eb2" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FinancialInstrumentAxis_4ff1af63-e166-42ea-94a4-03c266788a20" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_FinancialInstrumentAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_DebtSecuritiesAvailableForSaleTable_8500e2e6-9f2e-4028-953e-996112d28eb2" xlink:to="loc_us-gaap_FinancialInstrumentAxis_4ff1af63-e166-42ea-94a4-03c266788a20" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_4ff1af63-e166-42ea-94a4-03c266788a20_default" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_FinancialInstrumentAxis_4ff1af63-e166-42ea-94a4-03c266788a20" xlink:to="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_4ff1af63-e166-42ea-94a4-03c266788a20_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_63742584-300e-44a1-877f-5b88b6f6a35e" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_FinancialInstrumentAxis_4ff1af63-e166-42ea-94a4-03c266788a20" xlink:to="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_63742584-300e-44a1-877f-5b88b6f6a35e" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_MoneyMarketFundsMember_9154ba54-850c-48e9-bb96-15b380b88adf" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_MoneyMarketFundsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_63742584-300e-44a1-877f-5b88b6f6a35e" xlink:to="loc_us-gaap_MoneyMarketFundsMember_9154ba54-850c-48e9-bb96-15b380b88adf" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CertificatesOfDepositMember_b67a590e-e36f-403e-8383-bd3c883c44dd" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_CertificatesOfDepositMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_63742584-300e-44a1-877f-5b88b6f6a35e" xlink:to="loc_us-gaap_CertificatesOfDepositMember_b67a590e-e36f-403e-8383-bd3c883c44dd" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_BalanceSheetLocationAxis_c2668f32-4777-4a71-82b1-231a13fad30c" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_BalanceSheetLocationAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_DebtSecuritiesAvailableForSaleTable_8500e2e6-9f2e-4028-953e-996112d28eb2" xlink:to="loc_us-gaap_BalanceSheetLocationAxis_c2668f32-4777-4a71-82b1-231a13fad30c" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_BalanceSheetLocationDomain_c2668f32-4777-4a71-82b1-231a13fad30c_default" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_BalanceSheetLocationDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_BalanceSheetLocationAxis_c2668f32-4777-4a71-82b1-231a13fad30c" xlink:to="loc_us-gaap_BalanceSheetLocationDomain_c2668f32-4777-4a71-82b1-231a13fad30c_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_BalanceSheetLocationDomain_08017d25-6ed4-4580-91ac-43fd398abae3" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_BalanceSheetLocationDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_BalanceSheetLocationAxis_c2668f32-4777-4a71-82b1-231a13fad30c" xlink:to="loc_us-gaap_BalanceSheetLocationDomain_08017d25-6ed4-4580-91ac-43fd398abae3" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CashEquivalentsMember_22d9ecff-057b-4233-905d-1409328702e4" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_CashEquivalentsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_BalanceSheetLocationDomain_08017d25-6ed4-4580-91ac-43fd398abae3" xlink:to="loc_us-gaap_CashEquivalentsMember_22d9ecff-057b-4233-905d-1409328702e4" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AvailableForSaleDebtSecuritiesAmortizedCostBasis_a39565dd-c973-4386-9bc3-24efeac15953" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_AvailableForSaleDebtSecuritiesAmortizedCostBasis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ScheduleOfAvailableForSaleSecuritiesLineItems_20a39327-5072-42cd-a427-dd46c26e6be4" xlink:to="loc_us-gaap_AvailableForSaleDebtSecuritiesAmortizedCostBasis_a39565dd-c973-4386-9bc3-24efeac15953" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax_20f15084-95e2-48dd-98aa-cd62f796298f" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ScheduleOfAvailableForSaleSecuritiesLineItems_20a39327-5072-42cd-a427-dd46c26e6be4" xlink:to="loc_us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax_20f15084-95e2-48dd-98aa-cd62f796298f" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax_5207699c-6b44-4302-aea9-e18e38e39e46" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ScheduleOfAvailableForSaleSecuritiesLineItems_20a39327-5072-42cd-a427-dd46c26e6be4" xlink:to="loc_us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax_5207699c-6b44-4302-aea9-e18e38e39e46" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AvailableForSaleSecuritiesDebtSecurities_b08437f3-90ef-4d0d-9117-1fa129fc7eb0" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_AvailableForSaleSecuritiesDebtSecurities"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ScheduleOfAvailableForSaleSecuritiesLineItems_20a39327-5072-42cd-a427-dd46c26e6be4" xlink:to="loc_us-gaap_AvailableForSaleSecuritiesDebtSecurities_b08437f3-90ef-4d0d-9117-1fa129fc7eb0" xlink:type="arc" order="3"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.esperion.com/role/InvestmentsNarrativeDetails" xlink:type="simple" xlink:href="espr-20240331.xsd#InvestmentsNarrativeDetails"/>
  <link:definitionLink xlink:role="http://www.esperion.com/role/InvestmentsNarrativeDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfAvailableForSaleSecuritiesLineItems_2f919ebb-6d94-4e41-9887-86c2aefb44e1" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ScheduleOfAvailableForSaleSecuritiesLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtSecuritiesAvailableForSaleTable_8c73800d-da9f-4a0d-ac42-437c39d8cb0a" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_DebtSecuritiesAvailableForSaleTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_ScheduleOfAvailableForSaleSecuritiesLineItems_2f919ebb-6d94-4e41-9887-86c2aefb44e1" xlink:to="loc_us-gaap_DebtSecuritiesAvailableForSaleTable_8c73800d-da9f-4a0d-ac42-437c39d8cb0a" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncomeStatementLocationAxis_9086c610-6e9e-4ad5-a1bc-0fcbe5689115" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_IncomeStatementLocationAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_DebtSecuritiesAvailableForSaleTable_8c73800d-da9f-4a0d-ac42-437c39d8cb0a" xlink:to="loc_us-gaap_IncomeStatementLocationAxis_9086c610-6e9e-4ad5-a1bc-0fcbe5689115" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncomeStatementLocationDomain_9086c610-6e9e-4ad5-a1bc-0fcbe5689115_default" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_IncomeStatementLocationDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_IncomeStatementLocationAxis_9086c610-6e9e-4ad5-a1bc-0fcbe5689115" xlink:to="loc_us-gaap_IncomeStatementLocationDomain_9086c610-6e9e-4ad5-a1bc-0fcbe5689115_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncomeStatementLocationDomain_515748e2-bbc0-4e0a-8ac0-66705e2823ab" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_IncomeStatementLocationDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_IncomeStatementLocationAxis_9086c610-6e9e-4ad5-a1bc-0fcbe5689115" xlink:to="loc_us-gaap_IncomeStatementLocationDomain_515748e2-bbc0-4e0a-8ac0-66705e2823ab" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OtherNonoperatingIncomeExpenseMember_b4abef89-d6c3-4f65-98d8-ae86c4b703bb" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_OtherNonoperatingIncomeExpenseMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncomeStatementLocationDomain_515748e2-bbc0-4e0a-8ac0-66705e2823ab" xlink:to="loc_us-gaap_OtherNonoperatingIncomeExpenseMember_b4abef89-d6c3-4f65-98d8-ae86c4b703bb" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ReclassificationOutOfAccumulatedOtherComprehensiveIncomeAxis_0f15835a-9951-4471-9d7d-558c6fb82bd3" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ReclassificationOutOfAccumulatedOtherComprehensiveIncomeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_DebtSecuritiesAvailableForSaleTable_8c73800d-da9f-4a0d-ac42-437c39d8cb0a" xlink:to="loc_us-gaap_ReclassificationOutOfAccumulatedOtherComprehensiveIncomeAxis_0f15835a-9951-4471-9d7d-558c6fb82bd3" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ReclassificationOutOfAccumulatedOtherComprehensiveIncomeDomain_0f15835a-9951-4471-9d7d-558c6fb82bd3_default" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ReclassificationOutOfAccumulatedOtherComprehensiveIncomeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_ReclassificationOutOfAccumulatedOtherComprehensiveIncomeAxis_0f15835a-9951-4471-9d7d-558c6fb82bd3" xlink:to="loc_us-gaap_ReclassificationOutOfAccumulatedOtherComprehensiveIncomeDomain_0f15835a-9951-4471-9d7d-558c6fb82bd3_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ReclassificationOutOfAccumulatedOtherComprehensiveIncomeDomain_bb1ae9e6-936b-4470-bcdc-991ba8128d3b" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ReclassificationOutOfAccumulatedOtherComprehensiveIncomeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_ReclassificationOutOfAccumulatedOtherComprehensiveIncomeAxis_0f15835a-9951-4471-9d7d-558c6fb82bd3" xlink:to="loc_us-gaap_ReclassificationOutOfAccumulatedOtherComprehensiveIncomeDomain_bb1ae9e6-936b-4470-bcdc-991ba8128d3b" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ReclassificationOutOfAccumulatedOtherComprehensiveIncomeMember_0d0bf105-742b-4499-8bce-c72963331bfd" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ReclassificationOutOfAccumulatedOtherComprehensiveIncomeMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ReclassificationOutOfAccumulatedOtherComprehensiveIncomeDomain_bb1ae9e6-936b-4470-bcdc-991ba8128d3b" xlink:to="loc_us-gaap_ReclassificationOutOfAccumulatedOtherComprehensiveIncomeMember_0d0bf105-742b-4499-8bce-c72963331bfd" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_InvestmentIncomeInterest_8bcaf68b-a254-4cbc-aefd-6567458e6558" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_InvestmentIncomeInterest"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ScheduleOfAvailableForSaleSecuritiesLineItems_2f919ebb-6d94-4e41-9887-86c2aefb44e1" xlink:to="loc_us-gaap_InvestmentIncomeInterest_8bcaf68b-a254-4cbc-aefd-6567458e6558" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AccretionAmortizationOfDiscountsAndPremiumsInvestments_befa53a4-c98b-45a6-baff-d5b6e6f86c7f" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_AccretionAmortizationOfDiscountsAndPremiumsInvestments"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ScheduleOfAvailableForSaleSecuritiesLineItems_2f919ebb-6d94-4e41-9887-86c2aefb44e1" xlink:to="loc_us-gaap_AccretionAmortizationOfDiscountsAndPremiumsInvestments_befa53a4-c98b-45a6-baff-d5b6e6f86c7f" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OtherNonoperatingIncomeExpense_45b8a3d7-634c-493d-aa5c-106d8f1778cb" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_OtherNonoperatingIncomeExpense"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ScheduleOfAvailableForSaleSecuritiesLineItems_2f919ebb-6d94-4e41-9887-86c2aefb44e1" xlink:to="loc_us-gaap_OtherNonoperatingIncomeExpense_45b8a3d7-634c-493d-aa5c-106d8f1778cb" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtSecuritiesAvailableForSaleAllowanceForCreditLoss_83acecbc-d7b5-4297-ae11-ac178bb34d9c" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_DebtSecuritiesAvailableForSaleAllowanceForCreditLoss"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ScheduleOfAvailableForSaleSecuritiesLineItems_2f919ebb-6d94-4e41-9887-86c2aefb44e1" xlink:to="loc_us-gaap_DebtSecuritiesAvailableForSaleAllowanceForCreditLoss_83acecbc-d7b5-4297-ae11-ac178bb34d9c" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AccruedInvestmentIncomeReceivable_ecaf85f7-ac60-4477-b92a-6129744e6be5" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_AccruedInvestmentIncomeReceivable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ScheduleOfAvailableForSaleSecuritiesLineItems_2f919ebb-6d94-4e41-9887-86c2aefb44e1" xlink:to="loc_us-gaap_AccruedInvestmentIncomeReceivable_ecaf85f7-ac60-4477-b92a-6129744e6be5" xlink:type="arc" order="4"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.esperion.com/role/FairValueMeasurementsDetails" xlink:type="simple" xlink:href="espr-20240331.xsd#FairValueMeasurementsDetails"/>
  <link:definitionLink xlink:role="http://www.esperion.com/role/FairValueMeasurementsDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems_9332015e-cb89-4a9d-b651-29ee93e012bb" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable_2e7beef6-54e8-4350-add1-0ab45440bab6" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems_9332015e-cb89-4a9d-b651-29ee93e012bb" xlink:to="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable_2e7beef6-54e8-4350-add1-0ab45440bab6" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueByMeasurementFrequencyAxis_4e276b64-b8c0-4251-87a9-52e6c6da573d" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_FairValueByMeasurementFrequencyAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable_2e7beef6-54e8-4350-add1-0ab45440bab6" xlink:to="loc_us-gaap_FairValueByMeasurementFrequencyAxis_4e276b64-b8c0-4251-87a9-52e6c6da573d" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueMeasurementFrequencyDomain_4e276b64-b8c0-4251-87a9-52e6c6da573d_default" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_FairValueMeasurementFrequencyDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_FairValueByMeasurementFrequencyAxis_4e276b64-b8c0-4251-87a9-52e6c6da573d" xlink:to="loc_us-gaap_FairValueMeasurementFrequencyDomain_4e276b64-b8c0-4251-87a9-52e6c6da573d_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueMeasurementFrequencyDomain_d23b1707-358b-49e7-afb5-b993c0e3d30c" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_FairValueMeasurementFrequencyDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_FairValueByMeasurementFrequencyAxis_4e276b64-b8c0-4251-87a9-52e6c6da573d" xlink:to="loc_us-gaap_FairValueMeasurementFrequencyDomain_d23b1707-358b-49e7-afb5-b993c0e3d30c" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueMeasurementsRecurringMember_2e0823ed-c88b-4d2b-a2cf-690de1d1a5d4" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_FairValueMeasurementsRecurringMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FairValueMeasurementFrequencyDomain_d23b1707-358b-49e7-afb5-b993c0e3d30c" xlink:to="loc_us-gaap_FairValueMeasurementsRecurringMember_2e0823ed-c88b-4d2b-a2cf-690de1d1a5d4" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueByFairValueHierarchyLevelAxis_597f84db-3b88-4e99-b354-f1597c0aa8bd" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_FairValueByFairValueHierarchyLevelAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable_2e7beef6-54e8-4350-add1-0ab45440bab6" xlink:to="loc_us-gaap_FairValueByFairValueHierarchyLevelAxis_597f84db-3b88-4e99-b354-f1597c0aa8bd" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueMeasurementsFairValueHierarchyDomain_597f84db-3b88-4e99-b354-f1597c0aa8bd_default" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_FairValueMeasurementsFairValueHierarchyDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_FairValueByFairValueHierarchyLevelAxis_597f84db-3b88-4e99-b354-f1597c0aa8bd" xlink:to="loc_us-gaap_FairValueMeasurementsFairValueHierarchyDomain_597f84db-3b88-4e99-b354-f1597c0aa8bd_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueMeasurementsFairValueHierarchyDomain_93885f8f-06c1-4839-9d43-278f98b7bea4" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_FairValueMeasurementsFairValueHierarchyDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_FairValueByFairValueHierarchyLevelAxis_597f84db-3b88-4e99-b354-f1597c0aa8bd" xlink:to="loc_us-gaap_FairValueMeasurementsFairValueHierarchyDomain_93885f8f-06c1-4839-9d43-278f98b7bea4" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueInputsLevel1Member_561c7ab0-1e37-4e0b-a076-5eea684a9db7" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_FairValueInputsLevel1Member"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FairValueMeasurementsFairValueHierarchyDomain_93885f8f-06c1-4839-9d43-278f98b7bea4" xlink:to="loc_us-gaap_FairValueInputsLevel1Member_561c7ab0-1e37-4e0b-a076-5eea684a9db7" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueInputsLevel2Member_5296f4aa-e8a0-4b84-8063-2251df587f3f" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_FairValueInputsLevel2Member"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FairValueMeasurementsFairValueHierarchyDomain_93885f8f-06c1-4839-9d43-278f98b7bea4" xlink:to="loc_us-gaap_FairValueInputsLevel2Member_5296f4aa-e8a0-4b84-8063-2251df587f3f" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueInputsLevel3Member_275158bb-2391-4644-a058-f3a36a5e6ac3" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_FairValueInputsLevel3Member"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FairValueMeasurementsFairValueHierarchyDomain_93885f8f-06c1-4839-9d43-278f98b7bea4" xlink:to="loc_us-gaap_FairValueInputsLevel3Member_275158bb-2391-4644-a058-f3a36a5e6ac3" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FinancialInstrumentAxis_fa88838e-2024-416c-962d-7f6db6c58fcd" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_FinancialInstrumentAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable_2e7beef6-54e8-4350-add1-0ab45440bab6" xlink:to="loc_us-gaap_FinancialInstrumentAxis_fa88838e-2024-416c-962d-7f6db6c58fcd" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_fa88838e-2024-416c-962d-7f6db6c58fcd_default" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_FinancialInstrumentAxis_fa88838e-2024-416c-962d-7f6db6c58fcd" xlink:to="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_fa88838e-2024-416c-962d-7f6db6c58fcd_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_56659423-66bb-4bbc-8570-abb783243262" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_FinancialInstrumentAxis_fa88838e-2024-416c-962d-7f6db6c58fcd" xlink:to="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_56659423-66bb-4bbc-8570-abb783243262" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_MoneyMarketFundsMember_5df1bdcf-12cf-44dc-95db-b6ffc71453fb" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_MoneyMarketFundsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_56659423-66bb-4bbc-8570-abb783243262" xlink:to="loc_us-gaap_MoneyMarketFundsMember_5df1bdcf-12cf-44dc-95db-b6ffc71453fb" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CertificatesOfDepositMember_16dab758-52c5-4b0d-9b5c-0bc71bfd0d96" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_CertificatesOfDepositMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_56659423-66bb-4bbc-8570-abb783243262" xlink:to="loc_us-gaap_CertificatesOfDepositMember_16dab758-52c5-4b0d-9b5c-0bc71bfd0d96" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AssetsFairValueDisclosure_766647a3-2268-4da9-99b4-20ee1ce34c38" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_AssetsFairValueDisclosure"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems_9332015e-cb89-4a9d-b651-29ee93e012bb" xlink:to="loc_us-gaap_AssetsFairValueDisclosure_766647a3-2268-4da9-99b4-20ee1ce34c38" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_FairValueMeasurementAssetTransfersBetweenLevels_da634392-82cd-4e03-a2cf-7ae3478ad9d5" xlink:href="espr-20240331.xsd#espr_FairValueMeasurementAssetTransfersBetweenLevels"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems_9332015e-cb89-4a9d-b651-29ee93e012bb" xlink:to="loc_espr_FairValueMeasurementAssetTransfersBetweenLevels_da634392-82cd-4e03-a2cf-7ae3478ad9d5" xlink:type="arc" order="1"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.esperion.com/role/LiabilityRelatedtotheRevenueInterestPurchaseAgreementNarrativeDetails" xlink:type="simple" xlink:href="espr-20240331.xsd#LiabilityRelatedtotheRevenueInterestPurchaseAgreementNarrativeDetails"/>
  <link:definitionLink xlink:role="http://www.esperion.com/role/LiabilityRelatedtotheRevenueInterestPurchaseAgreementNarrativeDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_espr_LiabilityFromSaleOfFutureRevenuesLineItems_b2e2ea26-7100-487a-b911-74466fd825a8" xlink:href="espr-20240331.xsd#espr_LiabilityFromSaleOfFutureRevenuesLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_LiabilityFromSaleOfFutureRevenuesTable_efa8ce7f-dd39-4ab0-a1aa-9f4ea3d91732" xlink:href="espr-20240331.xsd#espr_LiabilityFromSaleOfFutureRevenuesTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_espr_LiabilityFromSaleOfFutureRevenuesLineItems_b2e2ea26-7100-487a-b911-74466fd825a8" xlink:to="loc_espr_LiabilityFromSaleOfFutureRevenuesTable_efa8ce7f-dd39-4ab0-a1aa-9f4ea3d91732" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_TypeOfArrangementAxis_ec7596cb-f278-437c-9cd5-c912d5ad0708" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_TypeOfArrangementAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_espr_LiabilityFromSaleOfFutureRevenuesTable_efa8ce7f-dd39-4ab0-a1aa-9f4ea3d91732" xlink:to="loc_us-gaap_TypeOfArrangementAxis_ec7596cb-f278-437c-9cd5-c912d5ad0708" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ArrangementsAndNonarrangementTransactionsMember_ec7596cb-f278-437c-9cd5-c912d5ad0708_default" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ArrangementsAndNonarrangementTransactionsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_TypeOfArrangementAxis_ec7596cb-f278-437c-9cd5-c912d5ad0708" xlink:to="loc_us-gaap_ArrangementsAndNonarrangementTransactionsMember_ec7596cb-f278-437c-9cd5-c912d5ad0708_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ArrangementsAndNonarrangementTransactionsMember_7871f558-868e-40dd-a9b7-da0af40a7b66" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ArrangementsAndNonarrangementTransactionsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_TypeOfArrangementAxis_ec7596cb-f278-437c-9cd5-c912d5ad0708" xlink:to="loc_us-gaap_ArrangementsAndNonarrangementTransactionsMember_7871f558-868e-40dd-a9b7-da0af40a7b66" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_RevenueInterestPurchaseAgreementMember_bbb051f8-995b-40df-9746-ec3099a0bc09" xlink:href="espr-20240331.xsd#espr_RevenueInterestPurchaseAgreementMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ArrangementsAndNonarrangementTransactionsMember_7871f558-868e-40dd-a9b7-da0af40a7b66" xlink:to="loc_espr_RevenueInterestPurchaseAgreementMember_bbb051f8-995b-40df-9746-ec3099a0bc09" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_RevenueInterestPurchaseAgreementAmendmentMember_a42dbf80-b0c2-489e-946b-2e0982ec2761" xlink:href="espr-20240331.xsd#espr_RevenueInterestPurchaseAgreementAmendmentMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ArrangementsAndNonarrangementTransactionsMember_7871f558-868e-40dd-a9b7-da0af40a7b66" xlink:to="loc_espr_RevenueInterestPurchaseAgreementAmendmentMember_a42dbf80-b0c2-489e-946b-2e0982ec2761" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_RIPAAmendmentToTheSecurityAgreementAndWaiverMember_8d69795f-afa1-49ff-9860-1e4c26e34d99" xlink:href="espr-20240331.xsd#espr_RIPAAmendmentToTheSecurityAgreementAndWaiverMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ArrangementsAndNonarrangementTransactionsMember_7871f558-868e-40dd-a9b7-da0af40a7b66" xlink:to="loc_espr_RIPAAmendmentToTheSecurityAgreementAndWaiverMember_8d69795f-afa1-49ff-9860-1e4c26e34d99" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_CounterpartyNameAxis_5ba5f07b-45f4-477d-93e2-e1d532f893fe" xlink:href="https://xbrl.fasb.org/srt/2023/elts/srt-2023.xsd#srt_CounterpartyNameAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_espr_LiabilityFromSaleOfFutureRevenuesTable_efa8ce7f-dd39-4ab0-a1aa-9f4ea3d91732" xlink:to="loc_srt_CounterpartyNameAxis_5ba5f07b-45f4-477d-93e2-e1d532f893fe" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RepurchaseAgreementCounterpartyNameDomain_5ba5f07b-45f4-477d-93e2-e1d532f893fe_default" xlink:href="https://xbrl.fasb.org/srt/2023/elts/srt-2023.xsd#srt_RepurchaseAgreementCounterpartyNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_CounterpartyNameAxis_5ba5f07b-45f4-477d-93e2-e1d532f893fe" xlink:to="loc_srt_RepurchaseAgreementCounterpartyNameDomain_5ba5f07b-45f4-477d-93e2-e1d532f893fe_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RepurchaseAgreementCounterpartyNameDomain_805c0b74-7d81-43c2-9d5d-cdf7ccf74a6d" xlink:href="https://xbrl.fasb.org/srt/2023/elts/srt-2023.xsd#srt_RepurchaseAgreementCounterpartyNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_CounterpartyNameAxis_5ba5f07b-45f4-477d-93e2-e1d532f893fe" xlink:to="loc_srt_RepurchaseAgreementCounterpartyNameDomain_805c0b74-7d81-43c2-9d5d-cdf7ccf74a6d" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_EigerIiiSaLlcMember_8976b3be-6598-4367-b222-7d134aaff3e9" xlink:href="espr-20240331.xsd#espr_EigerIiiSaLlcMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_RepurchaseAgreementCounterpartyNameDomain_805c0b74-7d81-43c2-9d5d-cdf7ccf74a6d" xlink:to="loc_espr_EigerIiiSaLlcMember_8976b3be-6598-4367-b222-7d134aaff3e9" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_NetSalesThresholdAxis_bf865e92-679f-4a6f-8801-e458d6c17b9e" xlink:href="espr-20240331.xsd#espr_NetSalesThresholdAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_espr_LiabilityFromSaleOfFutureRevenuesTable_efa8ce7f-dd39-4ab0-a1aa-9f4ea3d91732" xlink:to="loc_espr_NetSalesThresholdAxis_bf865e92-679f-4a6f-8801-e458d6c17b9e" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_NetSalesThresholdDomain_bf865e92-679f-4a6f-8801-e458d6c17b9e_default" xlink:href="espr-20240331.xsd#espr_NetSalesThresholdDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_espr_NetSalesThresholdAxis_bf865e92-679f-4a6f-8801-e458d6c17b9e" xlink:to="loc_espr_NetSalesThresholdDomain_bf865e92-679f-4a6f-8801-e458d6c17b9e_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_NetSalesThresholdDomain_9fe659e3-1472-4cee-ac8f-113a70585cfa" xlink:href="espr-20240331.xsd#espr_NetSalesThresholdDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_espr_NetSalesThresholdAxis_bf865e92-679f-4a6f-8801-e458d6c17b9e" xlink:to="loc_espr_NetSalesThresholdDomain_9fe659e3-1472-4cee-ac8f-113a70585cfa" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_NetSalesThresholdOneMember_2b5a8439-31b7-473e-8d62-6417be169d58" xlink:href="espr-20240331.xsd#espr_NetSalesThresholdOneMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_espr_NetSalesThresholdDomain_9fe659e3-1472-4cee-ac8f-113a70585cfa" xlink:to="loc_espr_NetSalesThresholdOneMember_2b5a8439-31b7-473e-8d62-6417be169d58" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_NetSalesThresholdTwoMember_baa53073-6e66-4167-a68d-3d8999a91e7a" xlink:href="espr-20240331.xsd#espr_NetSalesThresholdTwoMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_espr_NetSalesThresholdDomain_9fe659e3-1472-4cee-ac8f-113a70585cfa" xlink:to="loc_espr_NetSalesThresholdTwoMember_baa53073-6e66-4167-a68d-3d8999a91e7a" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_GrossProceedsFromRevenueInterestPurchaseAgreement_efd1aaeb-e7d8-4807-9dd4-164f76450266" xlink:href="espr-20240331.xsd#espr_GrossProceedsFromRevenueInterestPurchaseAgreement"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_espr_LiabilityFromSaleOfFutureRevenuesLineItems_b2e2ea26-7100-487a-b911-74466fd825a8" xlink:to="loc_espr_GrossProceedsFromRevenueInterestPurchaseAgreement_efd1aaeb-e7d8-4807-9dd4-164f76450266" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_AmountOfSubsequentInstallmentSubjectToRevenueInterestPurchaseAgreementTermsAndConditions_54ed1c01-33dc-4ccb-9fd2-0278e0861111" xlink:href="espr-20240331.xsd#espr_AmountOfSubsequentInstallmentSubjectToRevenueInterestPurchaseAgreementTermsAndConditions"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_espr_LiabilityFromSaleOfFutureRevenuesLineItems_b2e2ea26-7100-487a-b911-74466fd825a8" xlink:to="loc_espr_AmountOfSubsequentInstallmentSubjectToRevenueInterestPurchaseAgreementTermsAndConditions_54ed1c01-33dc-4ccb-9fd2-0278e0861111" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_AmountOfSubsequentInstallmentSubjectToRegulatoryApproval_dcc8baa2-7d5e-4f15-9c4d-29b4c021ef4f" xlink:href="espr-20240331.xsd#espr_AmountOfSubsequentInstallmentSubjectToRegulatoryApproval"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_espr_LiabilityFromSaleOfFutureRevenuesLineItems_b2e2ea26-7100-487a-b911-74466fd825a8" xlink:to="loc_espr_AmountOfSubsequentInstallmentSubjectToRegulatoryApproval_dcc8baa2-7d5e-4f15-9c4d-29b4c021ef4f" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_AmountOfSubsequentInstallmentSubjectToAchievementOfSalesThreshold_3b0dfc72-56d8-47ac-a9e8-f15401a90759" xlink:href="espr-20240331.xsd#espr_AmountOfSubsequentInstallmentSubjectToAchievementOfSalesThreshold"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_espr_LiabilityFromSaleOfFutureRevenuesLineItems_b2e2ea26-7100-487a-b911-74466fd825a8" xlink:to="loc_espr_AmountOfSubsequentInstallmentSubjectToAchievementOfSalesThreshold_3b0dfc72-56d8-47ac-a9e8-f15401a90759" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_MilestoneAmountForWorldwideSalesToReceiveThirdPayment_486768f2-8e8e-42fc-82d7-2b1ae9b2ca50" xlink:href="espr-20240331.xsd#espr_MilestoneAmountForWorldwideSalesToReceiveThirdPayment"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_espr_LiabilityFromSaleOfFutureRevenuesLineItems_b2e2ea26-7100-487a-b911-74466fd825a8" xlink:to="loc_espr_MilestoneAmountForWorldwideSalesToReceiveThirdPayment_486768f2-8e8e-42fc-82d7-2b1ae9b2ca50" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_ProceedsFromRevenueInterestPurchaseAgreement_65a22105-c9fc-4043-931a-3e06d555e8c7" xlink:href="espr-20240331.xsd#espr_ProceedsFromRevenueInterestPurchaseAgreement"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_espr_LiabilityFromSaleOfFutureRevenuesLineItems_b2e2ea26-7100-487a-b911-74466fd825a8" xlink:to="loc_espr_ProceedsFromRevenueInterestPurchaseAgreement_65a22105-c9fc-4043-931a-3e06d555e8c7" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_RevenueInterestRateTierTwo_fe5c34b3-3d2f-443b-8083-f3c5b560696c" xlink:href="espr-20240331.xsd#espr_RevenueInterestRateTierTwo"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_espr_LiabilityFromSaleOfFutureRevenuesLineItems_b2e2ea26-7100-487a-b911-74466fd825a8" xlink:to="loc_espr_RevenueInterestRateTierTwo_fe5c34b3-3d2f-443b-8083-f3c5b560696c" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_RevenueInterestRateInitialRate_3fcd9f7a-deb2-45cc-8ade-7dbe2b5773f5" xlink:href="espr-20240331.xsd#espr_RevenueInterestRateInitialRate"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_espr_LiabilityFromSaleOfFutureRevenuesLineItems_b2e2ea26-7100-487a-b911-74466fd825a8" xlink:to="loc_espr_RevenueInterestRateInitialRate_3fcd9f7a-deb2-45cc-8ade-7dbe2b5773f5" xlink:type="arc" order="7"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_PercentageOfInvestedCapitalReceivedByDecember312024ToQualifyForSecondReducedRevenueInterestRate_1f555872-449f-4c93-9d63-0d9c05b7f9d8" xlink:href="espr-20240331.xsd#espr_PercentageOfInvestedCapitalReceivedByDecember312024ToQualifyForSecondReducedRevenueInterestRate"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_espr_LiabilityFromSaleOfFutureRevenuesLineItems_b2e2ea26-7100-487a-b911-74466fd825a8" xlink:to="loc_espr_PercentageOfInvestedCapitalReceivedByDecember312024ToQualifyForSecondReducedRevenueInterestRate_1f555872-449f-4c93-9d63-0d9c05b7f9d8" xlink:type="arc" order="8"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_RevenueInterestRateTierThree_08d3041e-406e-42af-b7f3-d151db4dafa2" xlink:href="espr-20240331.xsd#espr_RevenueInterestRateTierThree"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_espr_LiabilityFromSaleOfFutureRevenuesLineItems_b2e2ea26-7100-487a-b911-74466fd825a8" xlink:to="loc_espr_RevenueInterestRateTierThree_08d3041e-406e-42af-b7f3-d151db4dafa2" xlink:type="arc" order="9"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_MinimumAmountOfAnnualNetSalesToQualifyForReducedRevenueInterestRate_182a287a-f614-4e84-8729-f7671fdc7433" xlink:href="espr-20240331.xsd#espr_MinimumAmountOfAnnualNetSalesToQualifyForReducedRevenueInterestRate"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_espr_LiabilityFromSaleOfFutureRevenuesLineItems_b2e2ea26-7100-487a-b911-74466fd825a8" xlink:to="loc_espr_MinimumAmountOfAnnualNetSalesToQualifyForReducedRevenueInterestRate_182a287a-f614-4e84-8729-f7671fdc7433" xlink:type="arc" order="10"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_PercentageOfRevenueInterestsPaymentOnWhichAgreementTerminates_bb02928c-5ea2-422b-908a-b78f7faf5344" xlink:href="espr-20240331.xsd#espr_PercentageOfRevenueInterestsPaymentOnWhichAgreementTerminates"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_espr_LiabilityFromSaleOfFutureRevenuesLineItems_b2e2ea26-7100-487a-b911-74466fd825a8" xlink:to="loc_espr_PercentageOfRevenueInterestsPaymentOnWhichAgreementTerminates_bb02928c-5ea2-422b-908a-b78f7faf5344" xlink:type="arc" order="11"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_TrailingNumberOfMonthsSalesMustBeAtOrAboveMilestoneAmount_908bcfab-81da-412b-900d-d237518a8e27" xlink:href="espr-20240331.xsd#espr_TrailingNumberOfMonthsSalesMustBeAtOrAboveMilestoneAmount"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_espr_LiabilityFromSaleOfFutureRevenuesLineItems_b2e2ea26-7100-487a-b911-74466fd825a8" xlink:to="loc_espr_TrailingNumberOfMonthsSalesMustBeAtOrAboveMilestoneAmount_908bcfab-81da-412b-900d-d237518a8e27" xlink:type="arc" order="12"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_MinimumAmountOfAnnualNetSalesToQualifyForReducedRevenueInterestRateContingentThreshold_4a861348-dbf1-4a94-8c9b-bf9a894f452d" xlink:href="espr-20240331.xsd#espr_MinimumAmountOfAnnualNetSalesToQualifyForReducedRevenueInterestRateContingentThreshold"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_espr_LiabilityFromSaleOfFutureRevenuesLineItems_b2e2ea26-7100-487a-b911-74466fd825a8" xlink:to="loc_espr_MinimumAmountOfAnnualNetSalesToQualifyForReducedRevenueInterestRateContingentThreshold_4a861348-dbf1-4a94-8c9b-bf9a894f452d" xlink:type="arc" order="13"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_PercentageOfRevenueInterestPaymentsReceivedByDecember312024ToQualifyForThirdPaymentApplicablePercentage_1577f66b-271b-424a-bca2-91478bd7e7cb" xlink:href="espr-20240331.xsd#espr_PercentageOfRevenueInterestPaymentsReceivedByDecember312024ToQualifyForThirdPaymentApplicablePercentage"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_espr_LiabilityFromSaleOfFutureRevenuesLineItems_b2e2ea26-7100-487a-b911-74466fd825a8" xlink:to="loc_espr_PercentageOfRevenueInterestPaymentsReceivedByDecember312024ToQualifyForThirdPaymentApplicablePercentage_1577f66b-271b-424a-bca2-91478bd7e7cb" xlink:type="arc" order="14"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_PercentageOfCumulativePurchaserPaymentsGuarantee_b553fd0b-e2e4-4a3f-9ffa-b6bd3fa2c2ef" xlink:href="espr-20240331.xsd#espr_PercentageOfCumulativePurchaserPaymentsGuarantee"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_espr_LiabilityFromSaleOfFutureRevenuesLineItems_b2e2ea26-7100-487a-b911-74466fd825a8" xlink:to="loc_espr_PercentageOfCumulativePurchaserPaymentsGuarantee_b553fd0b-e2e4-4a3f-9ffa-b6bd3fa2c2ef" xlink:type="arc" order="15"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_PercentageOfRevenueInterestsPaymentOnWhichAgreementTerminatesPriorToThirdAnniversaryOfClosingDateIfPutOptionIsExercised_05db6fbe-bb5d-4f76-8ee4-d68b0ceaeccf" xlink:href="espr-20240331.xsd#espr_PercentageOfRevenueInterestsPaymentOnWhichAgreementTerminatesPriorToThirdAnniversaryOfClosingDateIfPutOptionIsExercised"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_espr_LiabilityFromSaleOfFutureRevenuesLineItems_b2e2ea26-7100-487a-b911-74466fd825a8" xlink:to="loc_espr_PercentageOfRevenueInterestsPaymentOnWhichAgreementTerminatesPriorToThirdAnniversaryOfClosingDateIfPutOptionIsExercised_05db6fbe-bb5d-4f76-8ee4-d68b0ceaeccf" xlink:type="arc" order="16"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_PercentageOfRevenueInterestsPaymentOnWhichAgreementTerminatesAfterThirdAnniversaryOfClosingDateIfPutOptionIsExercised_bf0c31ed-da06-48bb-9601-6e4c95af95a3" xlink:href="espr-20240331.xsd#espr_PercentageOfRevenueInterestsPaymentOnWhichAgreementTerminatesAfterThirdAnniversaryOfClosingDateIfPutOptionIsExercised"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_espr_LiabilityFromSaleOfFutureRevenuesLineItems_b2e2ea26-7100-487a-b911-74466fd825a8" xlink:to="loc_espr_PercentageOfRevenueInterestsPaymentOnWhichAgreementTerminatesAfterThirdAnniversaryOfClosingDateIfPutOptionIsExercised_bf0c31ed-da06-48bb-9601-6e4c95af95a3" xlink:type="arc" order="17"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_SpecifiedNetRevenueThresholdTriggeringDepositInBlockedAccount_7969c818-0e96-4a7c-aa23-0f667229506d" xlink:href="espr-20240331.xsd#espr_SpecifiedNetRevenueThresholdTriggeringDepositInBlockedAccount"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_espr_LiabilityFromSaleOfFutureRevenuesLineItems_b2e2ea26-7100-487a-b911-74466fd825a8" xlink:to="loc_espr_SpecifiedNetRevenueThresholdTriggeringDepositInBlockedAccount_7969c818-0e96-4a7c-aa23-0f667229506d" xlink:type="arc" order="18"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_BlockedAccountDepositAmountIfSpecifiedNetRevenueDoesNotMeetThreshold_b61959e5-df4a-4354-bf26-afee77bb8e8e" xlink:href="espr-20240331.xsd#espr_BlockedAccountDepositAmountIfSpecifiedNetRevenueDoesNotMeetThreshold"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_espr_LiabilityFromSaleOfFutureRevenuesLineItems_b2e2ea26-7100-487a-b911-74466fd825a8" xlink:to="loc_espr_BlockedAccountDepositAmountIfSpecifiedNetRevenueDoesNotMeetThreshold_b61959e5-df4a-4354-bf26-afee77bb8e8e" xlink:type="arc" order="19"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RestrictedCash_4033fbeb-eb47-4691-bf75-269efa9df6fe" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_RestrictedCash"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_espr_LiabilityFromSaleOfFutureRevenuesLineItems_b2e2ea26-7100-487a-b911-74466fd825a8" xlink:to="loc_us-gaap_RestrictedCash_4033fbeb-eb47-4691-bf75-269efa9df6fe" xlink:type="arc" order="20"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_OneTimePartialCall_65e70db5-9f36-4b83-9e65-3b23acaa664d" xlink:href="espr-20240331.xsd#espr_OneTimePartialCall"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_espr_LiabilityFromSaleOfFutureRevenuesLineItems_b2e2ea26-7100-487a-b911-74466fd825a8" xlink:to="loc_espr_OneTimePartialCall_65e70db5-9f36-4b83-9e65-3b23acaa664d" xlink:type="arc" order="21"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_RevenueInterestsPaymentOnWhichAgreementTerminates_82d6658d-3c0c-42e4-a23e-9f3e62fe3c31" xlink:href="espr-20240331.xsd#espr_RevenueInterestsPaymentOnWhichAgreementTerminates"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_espr_LiabilityFromSaleOfFutureRevenuesLineItems_b2e2ea26-7100-487a-b911-74466fd825a8" xlink:to="loc_espr_RevenueInterestsPaymentOnWhichAgreementTerminates_82d6658d-3c0c-42e4-a23e-9f3e62fe3c31" xlink:type="arc" order="22"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_RevenueInterestLiability_fac49ae3-a0ac-45d8-b1b4-3754d0909e0c" xlink:href="espr-20240331.xsd#espr_RevenueInterestLiability"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_espr_LiabilityFromSaleOfFutureRevenuesLineItems_b2e2ea26-7100-487a-b911-74466fd825a8" xlink:to="loc_espr_RevenueInterestLiability_fac49ae3-a0ac-45d8-b1b4-3754d0909e0c" xlink:type="arc" order="23"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_UnamortizedTransactionCostsOnRevenueInterestAgreement_aab1414c-845e-4873-990e-4f55e9bfb872" xlink:href="espr-20240331.xsd#espr_UnamortizedTransactionCostsOnRevenueInterestAgreement"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_espr_LiabilityFromSaleOfFutureRevenuesLineItems_b2e2ea26-7100-487a-b911-74466fd825a8" xlink:to="loc_espr_UnamortizedTransactionCostsOnRevenueInterestAgreement_aab1414c-845e-4873-990e-4f55e9bfb872" xlink:type="arc" order="24"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_RevenueInterestPaymentsRedemptionPercentage_12a4a1fe-e1a6-4382-851d-cd8ad0c0fe5a" xlink:href="espr-20240331.xsd#espr_RevenueInterestPaymentsRedemptionPercentage"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_espr_LiabilityFromSaleOfFutureRevenuesLineItems_b2e2ea26-7100-487a-b911-74466fd825a8" xlink:to="loc_espr_RevenueInterestPaymentsRedemptionPercentage_12a4a1fe-e1a6-4382-851d-cd8ad0c0fe5a" xlink:type="arc" order="25"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_RevenueInterestPaymentsRedemptionValue_3955fdf6-cb28-49d6-bd2b-fd6b9407efe4" xlink:href="espr-20240331.xsd#espr_RevenueInterestPaymentsRedemptionValue"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_espr_LiabilityFromSaleOfFutureRevenuesLineItems_b2e2ea26-7100-487a-b911-74466fd825a8" xlink:to="loc_espr_RevenueInterestPaymentsRedemptionValue_3955fdf6-cb28-49d6-bd2b-fd6b9407efe4" xlink:type="arc" order="26"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_RevenueInterestPaymentsRemainingRedemptionValue_55e92b50-fff4-4ca4-9a06-e898c2aa4567" xlink:href="espr-20240331.xsd#espr_RevenueInterestPaymentsRemainingRedemptionValue"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_espr_LiabilityFromSaleOfFutureRevenuesLineItems_b2e2ea26-7100-487a-b911-74466fd825a8" xlink:to="loc_espr_RevenueInterestPaymentsRemainingRedemptionValue_55e92b50-fff4-4ca4-9a06-e898c2aa4567" xlink:type="arc" order="27"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_InterestExpense_4345f329-19cd-41c3-b512-d40bd027ff65" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_InterestExpense"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_espr_LiabilityFromSaleOfFutureRevenuesLineItems_b2e2ea26-7100-487a-b911-74466fd825a8" xlink:to="loc_us-gaap_InterestExpense_4345f329-19cd-41c3-b512-d40bd027ff65" xlink:type="arc" order="28"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_PercentageOfRevenueInterestsPaymentOnWhichAgreementTerminatesAfterThirdAnniversary_63651cf9-2afd-43a3-bc1a-c9469c573458" xlink:href="espr-20240331.xsd#espr_PercentageOfRevenueInterestsPaymentOnWhichAgreementTerminatesAfterThirdAnniversary"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_espr_LiabilityFromSaleOfFutureRevenuesLineItems_b2e2ea26-7100-487a-b911-74466fd825a8" xlink:to="loc_espr_PercentageOfRevenueInterestsPaymentOnWhichAgreementTerminatesAfterThirdAnniversary_63651cf9-2afd-43a3-bc1a-c9469c573458" xlink:type="arc" order="29"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_HypotheticalSalesGeneratedAmount_04d2728d-7829-4981-9e60-0bf785f20e3a" xlink:href="espr-20240331.xsd#espr_HypotheticalSalesGeneratedAmount"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_espr_LiabilityFromSaleOfFutureRevenuesLineItems_b2e2ea26-7100-487a-b911-74466fd825a8" xlink:to="loc_espr_HypotheticalSalesGeneratedAmount_04d2728d-7829-4981-9e60-0bf785f20e3a" xlink:type="arc" order="30"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_HypotheticalRepaymentObligationBasedOnSalesGenerated_984918ea-464a-46a4-aeec-e6115ec6ee60" xlink:href="espr-20240331.xsd#espr_HypotheticalRepaymentObligationBasedOnSalesGenerated"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_espr_LiabilityFromSaleOfFutureRevenuesLineItems_b2e2ea26-7100-487a-b911-74466fd825a8" xlink:to="loc_espr_HypotheticalRepaymentObligationBasedOnSalesGenerated_984918ea-464a-46a4-aeec-e6115ec6ee60" xlink:type="arc" order="31"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_NetSalesThresholdToIncludeWorldwideSalesInCoveredTerritory_3d739a4c-cc3c-40b7-a1da-0ef599e62cf4" xlink:href="espr-20240331.xsd#espr_NetSalesThresholdToIncludeWorldwideSalesInCoveredTerritory"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_espr_LiabilityFromSaleOfFutureRevenuesLineItems_b2e2ea26-7100-487a-b911-74466fd825a8" xlink:to="loc_espr_NetSalesThresholdToIncludeWorldwideSalesInCoveredTerritory_3d739a4c-cc3c-40b7-a1da-0ef599e62cf4" xlink:type="arc" order="32"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_RevenueInterestRepaymentObligationAmountExpectedInNextTwelveMonths_0cd7698a-6066-4875-8af0-e0d1697a4c07" xlink:href="espr-20240331.xsd#espr_RevenueInterestRepaymentObligationAmountExpectedInNextTwelveMonths"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_espr_LiabilityFromSaleOfFutureRevenuesLineItems_b2e2ea26-7100-487a-b911-74466fd825a8" xlink:to="loc_espr_RevenueInterestRepaymentObligationAmountExpectedInNextTwelveMonths_0cd7698a-6066-4875-8af0-e0d1697a4c07" xlink:type="arc" order="33"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_RevenueInterestPurchaseAgreementEffectiveAnnualImputedInterestRate_1f6acc7a-5316-4c38-acf3-cd764f07ce61" xlink:href="espr-20240331.xsd#espr_RevenueInterestPurchaseAgreementEffectiveAnnualImputedInterestRate"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_espr_LiabilityFromSaleOfFutureRevenuesLineItems_b2e2ea26-7100-487a-b911-74466fd825a8" xlink:to="loc_espr_RevenueInterestPurchaseAgreementEffectiveAnnualImputedInterestRate_1f6acc7a-5316-4c38-acf3-cd764f07ce61" xlink:type="arc" order="34"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_ConsecutiveNumberOfMonthsSalesMustBeAtOrAboveMilestoneAmount_94ab8d0f-d0fb-4a96-b29e-9501a21da09a" xlink:href="espr-20240331.xsd#espr_ConsecutiveNumberOfMonthsSalesMustBeAtOrAboveMilestoneAmount"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_espr_LiabilityFromSaleOfFutureRevenuesLineItems_b2e2ea26-7100-487a-b911-74466fd825a8" xlink:to="loc_espr_ConsecutiveNumberOfMonthsSalesMustBeAtOrAboveMilestoneAmount_94ab8d0f-d0fb-4a96-b29e-9501a21da09a" xlink:type="arc" order="35"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_PercentageOfIncreaseInRoyaltyRateUponDrawdownOfThirdPayment_fc11952a-de94-4d61-8e45-55e159fc57b9" xlink:href="espr-20240331.xsd#espr_PercentageOfIncreaseInRoyaltyRateUponDrawdownOfThirdPayment"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_espr_LiabilityFromSaleOfFutureRevenuesLineItems_b2e2ea26-7100-487a-b911-74466fd825a8" xlink:to="loc_espr_PercentageOfIncreaseInRoyaltyRateUponDrawdownOfThirdPayment_fc11952a-de94-4d61-8e45-55e159fc57b9" xlink:type="arc" order="36"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.esperion.com/role/LiabilityRelatedtotheRevenueInterestPurchaseAgreementSummaryofRevenueInterestLiabilityDetails" xlink:type="simple" xlink:href="espr-20240331.xsd#LiabilityRelatedtotheRevenueInterestPurchaseAgreementSummaryofRevenueInterestLiabilityDetails"/>
  <link:definitionLink xlink:role="http://www.esperion.com/role/LiabilityRelatedtotheRevenueInterestPurchaseAgreementSummaryofRevenueInterestLiabilityDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_espr_LiabilityFromSaleOfFutureRevenuesLineItems_11965de6-2390-4431-bb8b-6ad5c5158485" xlink:href="espr-20240331.xsd#espr_LiabilityFromSaleOfFutureRevenuesLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_LiabilityFromSaleOfFutureRevenuesTable_1d03c64f-ea3d-4281-9e7c-1401c6b20a4a" xlink:href="espr-20240331.xsd#espr_LiabilityFromSaleOfFutureRevenuesTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_espr_LiabilityFromSaleOfFutureRevenuesLineItems_11965de6-2390-4431-bb8b-6ad5c5158485" xlink:to="loc_espr_LiabilityFromSaleOfFutureRevenuesTable_1d03c64f-ea3d-4281-9e7c-1401c6b20a4a" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_TypeOfArrangementAxis_dcbbeaf4-8ae0-411a-a8b8-42928ad65698" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_TypeOfArrangementAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_espr_LiabilityFromSaleOfFutureRevenuesTable_1d03c64f-ea3d-4281-9e7c-1401c6b20a4a" xlink:to="loc_us-gaap_TypeOfArrangementAxis_dcbbeaf4-8ae0-411a-a8b8-42928ad65698" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ArrangementsAndNonarrangementTransactionsMember_dcbbeaf4-8ae0-411a-a8b8-42928ad65698_default" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ArrangementsAndNonarrangementTransactionsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_TypeOfArrangementAxis_dcbbeaf4-8ae0-411a-a8b8-42928ad65698" xlink:to="loc_us-gaap_ArrangementsAndNonarrangementTransactionsMember_dcbbeaf4-8ae0-411a-a8b8-42928ad65698_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ArrangementsAndNonarrangementTransactionsMember_d60e1326-7b1b-4a66-b9b2-95db72576d6d" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ArrangementsAndNonarrangementTransactionsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_TypeOfArrangementAxis_dcbbeaf4-8ae0-411a-a8b8-42928ad65698" xlink:to="loc_us-gaap_ArrangementsAndNonarrangementTransactionsMember_d60e1326-7b1b-4a66-b9b2-95db72576d6d" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_RevenueInterestPurchaseAgreementMember_0ddf57fe-5fbd-453c-aa6d-bb1251ff565f" xlink:href="espr-20240331.xsd#espr_RevenueInterestPurchaseAgreementMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ArrangementsAndNonarrangementTransactionsMember_d60e1326-7b1b-4a66-b9b2-95db72576d6d" xlink:to="loc_espr_RevenueInterestPurchaseAgreementMember_0ddf57fe-5fbd-453c-aa6d-bb1251ff565f" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_LiabilityFromSaleOfFutureRevenuesRollForward_5cd708dc-2d63-44a7-a585-85cfac975df8" xlink:href="espr-20240331.xsd#espr_LiabilityFromSaleOfFutureRevenuesRollForward"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_espr_LiabilityFromSaleOfFutureRevenuesLineItems_11965de6-2390-4431-bb8b-6ad5c5158485" xlink:to="loc_espr_LiabilityFromSaleOfFutureRevenuesRollForward_5cd708dc-2d63-44a7-a585-85cfac975df8" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_RevenueInterestLiability_79c65b55-1e62-447c-a660-aaf465a2b327" xlink:href="espr-20240331.xsd#espr_RevenueInterestLiability"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_espr_LiabilityFromSaleOfFutureRevenuesRollForward_5cd708dc-2d63-44a7-a585-85cfac975df8" xlink:to="loc_espr_RevenueInterestLiability_79c65b55-1e62-447c-a660-aaf465a2b327" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_RevenueInterestLiabilityIncreaseForInterestExpenseRecognized_86f8d17a-f60f-4016-a793-8ae2ecd3d654" xlink:href="espr-20240331.xsd#espr_RevenueInterestLiabilityIncreaseForInterestExpenseRecognized"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_espr_LiabilityFromSaleOfFutureRevenuesRollForward_5cd708dc-2d63-44a7-a585-85cfac975df8" xlink:to="loc_espr_RevenueInterestLiabilityIncreaseForInterestExpenseRecognized_86f8d17a-f60f-4016-a793-8ae2ecd3d654" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_PaymentsFromRevenueInterestPurchaseAgreement_e5740c0b-2d2a-424c-bfdc-2a87080661de" xlink:href="espr-20240331.xsd#espr_PaymentsFromRevenueInterestPurchaseAgreement"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_espr_LiabilityFromSaleOfFutureRevenuesRollForward_5cd708dc-2d63-44a7-a585-85cfac975df8" xlink:to="loc_espr_PaymentsFromRevenueInterestPurchaseAgreement_e5740c0b-2d2a-424c-bfdc-2a87080661de" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_RevenueInterestLiability_3b616e82-9f56-4f4b-b5a5-441a9a23f6eb" xlink:href="espr-20240331.xsd#espr_RevenueInterestLiability"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.esperion.com/role/ConvertibleNotesDetails" xlink:type="simple" xlink:href="espr-20240331.xsd#ConvertibleNotesDetails"/>
  <link:definitionLink xlink:role="http://www.esperion.com/role/ConvertibleNotesDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentLineItems_c0bdd2ba-baa8-48cb-954b-7479ccb377b7" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_DebtInstrumentLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentTable_007c82a0-bb4c-4f24-8a49-4cbb0da7011f" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_DebtInstrumentTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_DebtInstrumentLineItems_c0bdd2ba-baa8-48cb-954b-7479ccb377b7" xlink:to="loc_us-gaap_DebtInstrumentTable_007c82a0-bb4c-4f24-8a49-4cbb0da7011f" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentAxis_99840f8c-8895-4a64-b545-2332bb49322e" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_DebtInstrumentAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_DebtInstrumentTable_007c82a0-bb4c-4f24-8a49-4cbb0da7011f" xlink:to="loc_us-gaap_DebtInstrumentAxis_99840f8c-8895-4a64-b545-2332bb49322e" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentNameDomain_99840f8c-8895-4a64-b545-2332bb49322e_default" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_DebtInstrumentNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_DebtInstrumentAxis_99840f8c-8895-4a64-b545-2332bb49322e" xlink:to="loc_us-gaap_DebtInstrumentNameDomain_99840f8c-8895-4a64-b545-2332bb49322e_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentNameDomain_114cd652-5c7d-4b66-a424-49fdcddd5a55" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_DebtInstrumentNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_DebtInstrumentAxis_99840f8c-8895-4a64-b545-2332bb49322e" xlink:to="loc_us-gaap_DebtInstrumentNameDomain_114cd652-5c7d-4b66-a424-49fdcddd5a55" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_ConvertibleSeniorNotesDue2025Member_044f1918-34ae-41d1-802f-f1f82b228245" xlink:href="espr-20240331.xsd#espr_ConvertibleSeniorNotesDue2025Member"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentNameDomain_114cd652-5c7d-4b66-a424-49fdcddd5a55" xlink:to="loc_espr_ConvertibleSeniorNotesDue2025Member_044f1918-34ae-41d1-802f-f1f82b228245" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LongtermDebtTypeAxis_252913d8-335e-42cd-8807-7453d1114e5e" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_LongtermDebtTypeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_DebtInstrumentTable_007c82a0-bb4c-4f24-8a49-4cbb0da7011f" xlink:to="loc_us-gaap_LongtermDebtTypeAxis_252913d8-335e-42cd-8807-7453d1114e5e" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LongtermDebtTypeDomain_252913d8-335e-42cd-8807-7453d1114e5e_default" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_LongtermDebtTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_LongtermDebtTypeAxis_252913d8-335e-42cd-8807-7453d1114e5e" xlink:to="loc_us-gaap_LongtermDebtTypeDomain_252913d8-335e-42cd-8807-7453d1114e5e_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LongtermDebtTypeDomain_1aaa88fc-2aff-4de4-a8c6-2db27577f213" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_LongtermDebtTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_LongtermDebtTypeAxis_252913d8-335e-42cd-8807-7453d1114e5e" xlink:to="loc_us-gaap_LongtermDebtTypeDomain_1aaa88fc-2aff-4de4-a8c6-2db27577f213" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ConvertibleDebtMember_15888e17-5706-429b-a1de-6a70cb64aaa7" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ConvertibleDebtMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LongtermDebtTypeDomain_1aaa88fc-2aff-4de4-a8c6-2db27577f213" xlink:to="loc_us-gaap_ConvertibleDebtMember_15888e17-5706-429b-a1de-6a70cb64aaa7" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentRedemptionPeriodAxis_bb2f96d8-f713-48ea-927a-1e29cdfdad48" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_DebtInstrumentRedemptionPeriodAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_DebtInstrumentTable_007c82a0-bb4c-4f24-8a49-4cbb0da7011f" xlink:to="loc_us-gaap_DebtInstrumentRedemptionPeriodAxis_bb2f96d8-f713-48ea-927a-1e29cdfdad48" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentRedemptionPeriodDomain_bb2f96d8-f713-48ea-927a-1e29cdfdad48_default" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_DebtInstrumentRedemptionPeriodDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_DebtInstrumentRedemptionPeriodAxis_bb2f96d8-f713-48ea-927a-1e29cdfdad48" xlink:to="loc_us-gaap_DebtInstrumentRedemptionPeriodDomain_bb2f96d8-f713-48ea-927a-1e29cdfdad48_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentRedemptionPeriodDomain_4f24a02f-86f7-41f1-809b-18a01cb49055" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_DebtInstrumentRedemptionPeriodDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_DebtInstrumentRedemptionPeriodAxis_bb2f96d8-f713-48ea-927a-1e29cdfdad48" xlink:to="loc_us-gaap_DebtInstrumentRedemptionPeriodDomain_4f24a02f-86f7-41f1-809b-18a01cb49055" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentRedemptionPeriodOneMember_23b5cfaa-9f4b-49ae-8f5b-94acb1c0ccd7" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_DebtInstrumentRedemptionPeriodOneMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentRedemptionPeriodDomain_4f24a02f-86f7-41f1-809b-18a01cb49055" xlink:to="loc_us-gaap_DebtInstrumentRedemptionPeriodOneMember_23b5cfaa-9f4b-49ae-8f5b-94acb1c0ccd7" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentRedemptionPeriodTwoMember_6a7fe573-db34-4c47-b46d-cc075c3464d8" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_DebtInstrumentRedemptionPeriodTwoMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentRedemptionPeriodDomain_4f24a02f-86f7-41f1-809b-18a01cb49055" xlink:to="loc_us-gaap_DebtInstrumentRedemptionPeriodTwoMember_6a7fe573-db34-4c47-b46d-cc075c3464d8" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ClassOfWarrantOrRightAxis_2c141fc7-ae67-4759-b6c0-0742296384f9" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ClassOfWarrantOrRightAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_DebtInstrumentTable_007c82a0-bb4c-4f24-8a49-4cbb0da7011f" xlink:to="loc_us-gaap_ClassOfWarrantOrRightAxis_2c141fc7-ae67-4759-b6c0-0742296384f9" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ClassOfWarrantOrRightDomain_2c141fc7-ae67-4759-b6c0-0742296384f9_default" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ClassOfWarrantOrRightDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_ClassOfWarrantOrRightAxis_2c141fc7-ae67-4759-b6c0-0742296384f9" xlink:to="loc_us-gaap_ClassOfWarrantOrRightDomain_2c141fc7-ae67-4759-b6c0-0742296384f9_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ClassOfWarrantOrRightDomain_1732ad2a-be0d-4457-b8a1-00fdc357f760" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ClassOfWarrantOrRightDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_ClassOfWarrantOrRightAxis_2c141fc7-ae67-4759-b6c0-0742296384f9" xlink:to="loc_us-gaap_ClassOfWarrantOrRightDomain_1732ad2a-be0d-4457-b8a1-00fdc357f760" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_CappedCallMember_97d3ca25-b013-416d-aad1-ee34dc4db16e" xlink:href="espr-20240331.xsd#espr_CappedCallMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfWarrantOrRightDomain_1732ad2a-be0d-4457-b8a1-00fdc357f760" xlink:to="loc_espr_CappedCallMember_97d3ca25-b013-416d-aad1-ee34dc4db16e" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StatementClassOfStockAxis_f41662d1-aca4-4271-b64e-a33a93da2403" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_StatementClassOfStockAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_DebtInstrumentTable_007c82a0-bb4c-4f24-8a49-4cbb0da7011f" xlink:to="loc_us-gaap_StatementClassOfStockAxis_f41662d1-aca4-4271-b64e-a33a93da2403" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ClassOfStockDomain_f41662d1-aca4-4271-b64e-a33a93da2403_default" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ClassOfStockDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_StatementClassOfStockAxis_f41662d1-aca4-4271-b64e-a33a93da2403" xlink:to="loc_us-gaap_ClassOfStockDomain_f41662d1-aca4-4271-b64e-a33a93da2403_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ClassOfStockDomain_a177d0dd-3158-4c03-a940-a97dac783645" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ClassOfStockDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_StatementClassOfStockAxis_f41662d1-aca4-4271-b64e-a33a93da2403" xlink:to="loc_us-gaap_ClassOfStockDomain_a177d0dd-3158-4c03-a940-a97dac783645" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CommonClassAMember_3998b809-de64-42a4-9741-6a4cc8b20623" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_CommonClassAMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfStockDomain_a177d0dd-3158-4c03-a940-a97dac783645" xlink:to="loc_us-gaap_CommonClassAMember_3998b809-de64-42a4-9741-6a4cc8b20623" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_NatureOfExpenseAxis_217f7109-4adc-427d-9bb8-ff8820130c0b" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_NatureOfExpenseAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_DebtInstrumentTable_007c82a0-bb4c-4f24-8a49-4cbb0da7011f" xlink:to="loc_us-gaap_NatureOfExpenseAxis_217f7109-4adc-427d-9bb8-ff8820130c0b" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_InterimPeriodCostsNotAllocableDomain_217f7109-4adc-427d-9bb8-ff8820130c0b_default" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_InterimPeriodCostsNotAllocableDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_NatureOfExpenseAxis_217f7109-4adc-427d-9bb8-ff8820130c0b" xlink:to="loc_us-gaap_InterimPeriodCostsNotAllocableDomain_217f7109-4adc-427d-9bb8-ff8820130c0b_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_InterimPeriodCostsNotAllocableDomain_d054c515-e520-4fe0-975f-95cfcf729602" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_InterimPeriodCostsNotAllocableDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_NatureOfExpenseAxis_217f7109-4adc-427d-9bb8-ff8820130c0b" xlink:to="loc_us-gaap_InterimPeriodCostsNotAllocableDomain_d054c515-e520-4fe0-975f-95cfcf729602" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_PurchaserDiscountsAndCommissionsAndOfferingExpensesPayableMember_3f2b3f90-c909-4476-8dec-160ef69e3862" xlink:href="espr-20240331.xsd#espr_PurchaserDiscountsAndCommissionsAndOfferingExpensesPayableMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_InterimPeriodCostsNotAllocableDomain_d054c515-e520-4fe0-975f-95cfcf729602" xlink:to="loc_espr_PurchaserDiscountsAndCommissionsAndOfferingExpensesPayableMember_3f2b3f90-c909-4476-8dec-160ef69e3862" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentFaceAmount_b8a42aeb-6090-49ae-b83b-dc68a19c4ed2" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_DebtInstrumentFaceAmount"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_c0bdd2ba-baa8-48cb-954b-7479ccb377b7" xlink:to="loc_us-gaap_DebtInstrumentFaceAmount_b8a42aeb-6090-49ae-b83b-dc68a19c4ed2" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentInterestRateStatedPercentage_60ef4bd6-82f9-4d3a-9cad-c468211ff7de" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_DebtInstrumentInterestRateStatedPercentage"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_c0bdd2ba-baa8-48cb-954b-7479ccb377b7" xlink:to="loc_us-gaap_DebtInstrumentInterestRateStatedPercentage_60ef4bd6-82f9-4d3a-9cad-c468211ff7de" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ProceedsFromDebtNetOfIssuanceCosts_4b2d9fc0-221d-4b49-aadc-dd0f70265e47" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ProceedsFromDebtNetOfIssuanceCosts"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_c0bdd2ba-baa8-48cb-954b-7479ccb377b7" xlink:to="loc_us-gaap_ProceedsFromDebtNetOfIssuanceCosts_4b2d9fc0-221d-4b49-aadc-dd0f70265e47" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DeferredFinanceCostsNet_1dcdb12e-7f64-4ea7-af5c-0a32b90e51e1" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_DeferredFinanceCostsNet"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_c0bdd2ba-baa8-48cb-954b-7479ccb377b7" xlink:to="loc_us-gaap_DeferredFinanceCostsNet_1dcdb12e-7f64-4ea7-af5c-0a32b90e51e1" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PaymentsForDerivativeInstrumentFinancingActivities_54476e6a-4570-47fd-a4ae-ab2963692d61" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_PaymentsForDerivativeInstrumentFinancingActivities"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_c0bdd2ba-baa8-48cb-954b-7479ccb377b7" xlink:to="loc_us-gaap_PaymentsForDerivativeInstrumentFinancingActivities_54476e6a-4570-47fd-a4ae-ab2963692d61" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PaymentsForRepurchaseOfCommonStock_21916ff4-e7df-4a1c-bdc2-6846213e4857" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_PaymentsForRepurchaseOfCommonStock"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_c0bdd2ba-baa8-48cb-954b-7479ccb377b7" xlink:to="loc_us-gaap_PaymentsForRepurchaseOfCommonStock_21916ff4-e7df-4a1c-bdc2-6846213e4857" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentConvertibleConversionRatio1_b8621f2f-aad0-43fb-9b2e-6601eb2d0739" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_DebtInstrumentConvertibleConversionRatio1"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_c0bdd2ba-baa8-48cb-954b-7479ccb377b7" xlink:to="loc_us-gaap_DebtInstrumentConvertibleConversionRatio1_b8621f2f-aad0-43fb-9b2e-6601eb2d0739" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentConvertibleConversionPrice1_210dd40f-759a-4b23-bfc4-a11a11bca883" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_DebtInstrumentConvertibleConversionPrice1"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_c0bdd2ba-baa8-48cb-954b-7479ccb377b7" xlink:to="loc_us-gaap_DebtInstrumentConvertibleConversionPrice1_210dd40f-759a-4b23-bfc4-a11a11bca883" xlink:type="arc" order="7"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentConvertibleThresholdPercentageOfStockPriceTrigger_12e9e826-5345-4481-90fb-7c4a8465f4d2" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_DebtInstrumentConvertibleThresholdPercentageOfStockPriceTrigger"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_c0bdd2ba-baa8-48cb-954b-7479ccb377b7" xlink:to="loc_us-gaap_DebtInstrumentConvertibleThresholdPercentageOfStockPriceTrigger_12e9e826-5345-4481-90fb-7c4a8465f4d2" xlink:type="arc" order="8"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentConvertibleThresholdTradingDays_0461197c-8a0a-4dbc-a41a-5c7fc4696a80" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_DebtInstrumentConvertibleThresholdTradingDays"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_c0bdd2ba-baa8-48cb-954b-7479ccb377b7" xlink:to="loc_us-gaap_DebtInstrumentConvertibleThresholdTradingDays_0461197c-8a0a-4dbc-a41a-5c7fc4696a80" xlink:type="arc" order="9"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentConvertibleThresholdConsecutiveTradingDays1_7431c327-e97a-444d-a6b9-1587fc968eeb" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_DebtInstrumentConvertibleThresholdConsecutiveTradingDays1"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_c0bdd2ba-baa8-48cb-954b-7479ccb377b7" xlink:to="loc_us-gaap_DebtInstrumentConvertibleThresholdConsecutiveTradingDays1_7431c327-e97a-444d-a6b9-1587fc968eeb" xlink:type="arc" order="10"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_NumberOfBusinessDays_b8d11aae-315a-41a8-b06c-140ad31627e5" xlink:href="espr-20240331.xsd#espr_NumberOfBusinessDays"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_c0bdd2ba-baa8-48cb-954b-7479ccb377b7" xlink:to="loc_espr_NumberOfBusinessDays_b8d11aae-315a-41a8-b06c-140ad31627e5" xlink:type="arc" order="11"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_NumberOfConsecutiveTradingDays_06dad0bb-c9b4-4695-9345-c67bf8f6820d" xlink:href="espr-20240331.xsd#espr_NumberOfConsecutiveTradingDays"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_c0bdd2ba-baa8-48cb-954b-7479ccb377b7" xlink:to="loc_espr_NumberOfConsecutiveTradingDays_06dad0bb-c9b4-4695-9345-c67bf8f6820d" xlink:type="arc" order="12"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_DebtInstrumentConvertibleThresholdPercentageOfLastReportedSalePrice_51db8457-2698-4cca-bb06-08c5bc326c81" xlink:href="espr-20240331.xsd#espr_DebtInstrumentConvertibleThresholdPercentageOfLastReportedSalePrice"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_c0bdd2ba-baa8-48cb-954b-7479ccb377b7" xlink:to="loc_espr_DebtInstrumentConvertibleThresholdPercentageOfLastReportedSalePrice_51db8457-2698-4cca-bb06-08c5bc326c81" xlink:type="arc" order="13"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentRedemptionPricePercentage_26dc5bc4-73fa-46ea-b99d-e8a94069c67f" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_DebtInstrumentRedemptionPricePercentage"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_c0bdd2ba-baa8-48cb-954b-7479ccb377b7" xlink:to="loc_us-gaap_DebtInstrumentRedemptionPricePercentage_26dc5bc4-73fa-46ea-b99d-e8a94069c67f" xlink:type="arc" order="14"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_DebtInstrumentCovenantRequiredAmountOutstanding_58e20f9c-04f1-4b4b-8214-ca4d2e664a69" xlink:href="espr-20240331.xsd#espr_DebtInstrumentCovenantRequiredAmountOutstanding"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_c0bdd2ba-baa8-48cb-954b-7479ccb377b7" xlink:to="loc_espr_DebtInstrumentCovenantRequiredAmountOutstanding_58e20f9c-04f1-4b4b-8214-ca4d2e664a69" xlink:type="arc" order="15"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtConversionConvertedInstrumentAmount1_65977866-a6ed-46e5-b648-fd3788256668" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_DebtConversionConvertedInstrumentAmount1"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_c0bdd2ba-baa8-48cb-954b-7479ccb377b7" xlink:to="loc_us-gaap_DebtConversionConvertedInstrumentAmount1_65977866-a6ed-46e5-b648-fd3788256668" xlink:type="arc" order="16"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_DebtInstrumentExchangeAgreementConversionWeightedAveragePricePerShareFloor_5c3174b1-83cf-41ae-81ec-6e07cf780e83" xlink:href="espr-20240331.xsd#espr_DebtInstrumentExchangeAgreementConversionWeightedAveragePricePerShareFloor"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_c0bdd2ba-baa8-48cb-954b-7479ccb377b7" xlink:to="loc_espr_DebtInstrumentExchangeAgreementConversionWeightedAveragePricePerShareFloor_5c3174b1-83cf-41ae-81ec-6e07cf780e83" xlink:type="arc" order="17"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_DebtInstrumentExchangeAgreementConvertibleThresholdTradingDays_49ecb957-44f8-4741-a82f-7d97bbab08fd" xlink:href="espr-20240331.xsd#espr_DebtInstrumentExchangeAgreementConvertibleThresholdTradingDays"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_c0bdd2ba-baa8-48cb-954b-7479ccb377b7" xlink:to="loc_espr_DebtInstrumentExchangeAgreementConvertibleThresholdTradingDays_49ecb957-44f8-4741-a82f-7d97bbab08fd" xlink:type="arc" order="18"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtConversionConvertedInstrumentSharesIssued1_4b4b1936-592c-4ed0-8bba-a1987fd5353f" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_DebtConversionConvertedInstrumentSharesIssued1"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_c0bdd2ba-baa8-48cb-954b-7479ccb377b7" xlink:to="loc_us-gaap_DebtConversionConvertedInstrumentSharesIssued1_4b4b1936-592c-4ed0-8bba-a1987fd5353f" xlink:type="arc" order="19"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentCarryingAmount_829f8b5a-1673-4df7-959d-dacbab9c28fd" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_DebtInstrumentCarryingAmount"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_c0bdd2ba-baa8-48cb-954b-7479ccb377b7" xlink:to="loc_us-gaap_DebtInstrumentCarryingAmount_829f8b5a-1673-4df7-959d-dacbab9c28fd" xlink:type="arc" order="20"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DeferredFinanceCostsGross_d5e0744f-df39-4123-9003-299ca049a334" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_DeferredFinanceCostsGross"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_c0bdd2ba-baa8-48cb-954b-7479ccb377b7" xlink:to="loc_us-gaap_DeferredFinanceCostsGross_d5e0744f-df39-4123-9003-299ca049a334" xlink:type="arc" order="21"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LongTermDebt_d35671bd-fd89-4a75-accb-ef419c3cb391" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_LongTermDebt"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_c0bdd2ba-baa8-48cb-954b-7479ccb377b7" xlink:to="loc_us-gaap_LongTermDebt_d35671bd-fd89-4a75-accb-ef419c3cb391" xlink:type="arc" order="22"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_InterestExpenseDebt_43c4cd32-907b-4dca-a382-ca27aaee362e" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_InterestExpenseDebt"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_c0bdd2ba-baa8-48cb-954b-7479ccb377b7" xlink:to="loc_us-gaap_InterestExpenseDebt_43c4cd32-907b-4dca-a382-ca27aaee362e" xlink:type="arc" order="23"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentFairValue_5a7bcd14-de3c-4b4c-a29e-d86f1adefebc" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_DebtInstrumentFairValue"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_c0bdd2ba-baa8-48cb-954b-7479ccb377b7" xlink:to="loc_us-gaap_DebtInstrumentFairValue_5a7bcd14-de3c-4b4c-a29e-d86f1adefebc" xlink:type="arc" order="24"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ClassOfWarrantOrRightExercisePriceOfWarrantsOrRights1_559ad76f-9f36-4e2e-9d31-50ef63122897" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ClassOfWarrantOrRightExercisePriceOfWarrantsOrRights1"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_c0bdd2ba-baa8-48cb-954b-7479ccb377b7" xlink:to="loc_us-gaap_ClassOfWarrantOrRightExercisePriceOfWarrantsOrRights1_559ad76f-9f36-4e2e-9d31-50ef63122897" xlink:type="arc" order="25"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_ClassOfWarrantOrRightExercisePriceOfWarrantsOrRightsPremiumPercentage_1b45c789-1aca-4f24-b04a-c847d3a686d1" xlink:href="espr-20240331.xsd#espr_ClassOfWarrantOrRightExercisePriceOfWarrantsOrRightsPremiumPercentage"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_c0bdd2ba-baa8-48cb-954b-7479ccb377b7" xlink:to="loc_espr_ClassOfWarrantOrRightExercisePriceOfWarrantsOrRightsPremiumPercentage_1b45c789-1aca-4f24-b04a-c847d3a686d1" xlink:type="arc" order="26"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_TreasuryStockSharesAcquired_55b7e226-b7b0-4fe5-975d-459bda88ce7c" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_TreasuryStockSharesAcquired"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_c0bdd2ba-baa8-48cb-954b-7479ccb377b7" xlink:to="loc_us-gaap_TreasuryStockSharesAcquired_55b7e226-b7b0-4fe5-975d-459bda88ce7c" xlink:type="arc" order="27"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StockIssuedDuringPeriodSharesTreasuryStockReissued_f954820d-d5f0-49d7-978c-f30dd8291cb0" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_StockIssuedDuringPeriodSharesTreasuryStockReissued"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_c0bdd2ba-baa8-48cb-954b-7479ccb377b7" xlink:to="loc_us-gaap_StockIssuedDuringPeriodSharesTreasuryStockReissued_f954820d-d5f0-49d7-978c-f30dd8291cb0" xlink:type="arc" order="28"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.esperion.com/role/StockCompensationStockOptionsAdditionalInformationDetails" xlink:type="simple" xlink:href="espr-20240331.xsd#StockCompensationStockOptionsAdditionalInformationDetails"/>
  <link:definitionLink xlink:role="http://www.esperion.com/role/StockCompensationStockOptionsAdditionalInformationDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_7770403c-ad11-4e91-903f-347944712685" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_bdeebd71-545c-483f-8722-69fa056d5c28" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_7770403c-ad11-4e91-903f-347944712685" xlink:to="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_bdeebd71-545c-483f-8722-69fa056d5c28" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AwardTypeAxis_dfca2913-c40c-4745-8ab1-b2fc97808d60" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_AwardTypeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_bdeebd71-545c-483f-8722-69fa056d5c28" xlink:to="loc_us-gaap_AwardTypeAxis_dfca2913-c40c-4745-8ab1-b2fc97808d60" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_dfca2913-c40c-4745-8ab1-b2fc97808d60_default" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_AwardTypeAxis_dfca2913-c40c-4745-8ab1-b2fc97808d60" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_dfca2913-c40c-4745-8ab1-b2fc97808d60_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_0730f279-b540-4e01-a591-db4a07be7e2d" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_AwardTypeAxis_dfca2913-c40c-4745-8ab1-b2fc97808d60" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_0730f279-b540-4e01-a591-db4a07be7e2d" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EmployeeStockMember_80358add-51db-4d4e-889e-4b2bf86d507d" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_EmployeeStockMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_0730f279-b540-4e01-a591-db4a07be7e2d" xlink:to="loc_us-gaap_EmployeeStockMember_80358add-51db-4d4e-889e-4b2bf86d507d" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EmployeeStockOptionMember_16610ab7-60fd-40f7-964e-dc3cdd5b4334" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_EmployeeStockOptionMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_0730f279-b540-4e01-a591-db4a07be7e2d" xlink:to="loc_us-gaap_EmployeeStockOptionMember_16610ab7-60fd-40f7-964e-dc3cdd5b4334" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_ShareBasedPaymentArrangementOptionPerformanceBasedMember_629b4d50-b451-46bb-94a8-8451f8e2b43a" xlink:href="espr-20240331.xsd#espr_ShareBasedPaymentArrangementOptionPerformanceBasedMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_0730f279-b540-4e01-a591-db4a07be7e2d" xlink:to="loc_espr_ShareBasedPaymentArrangementOptionPerformanceBasedMember_629b4d50-b451-46bb-94a8-8451f8e2b43a" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RestrictedStockUnitsRSUMember_2f45a072-5c94-4d8b-b50a-93791ebe03c8" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_RestrictedStockUnitsRSUMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_0730f279-b540-4e01-a591-db4a07be7e2d" xlink:to="loc_us-gaap_RestrictedStockUnitsRSUMember_2f45a072-5c94-4d8b-b50a-93791ebe03c8" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PerformanceSharesMember_1b9ec737-0db2-499f-a3d1-d79e6a577f9d" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_PerformanceSharesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_0730f279-b540-4e01-a591-db4a07be7e2d" xlink:to="loc_us-gaap_PerformanceSharesMember_1b9ec737-0db2-499f-a3d1-d79e6a577f9d" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PlanNameAxis_d78f3ede-ac87-4916-99f3-983784c8f935" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_PlanNameAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_bdeebd71-545c-483f-8722-69fa056d5c28" xlink:to="loc_us-gaap_PlanNameAxis_d78f3ede-ac87-4916-99f3-983784c8f935" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PlanNameDomain_d78f3ede-ac87-4916-99f3-983784c8f935_default" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_PlanNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_PlanNameAxis_d78f3ede-ac87-4916-99f3-983784c8f935" xlink:to="loc_us-gaap_PlanNameDomain_d78f3ede-ac87-4916-99f3-983784c8f935_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PlanNameDomain_721f84af-c676-472c-99bb-4c5a14225440" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_PlanNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_PlanNameAxis_d78f3ede-ac87-4916-99f3-983784c8f935" xlink:to="loc_us-gaap_PlanNameDomain_721f84af-c676-472c-99bb-4c5a14225440" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_StockOptionAndIncentivePlan2022Member_94d73515-eb38-49b0-96a3-769ed90f9a00" xlink:href="espr-20240331.xsd#espr_StockOptionAndIncentivePlan2022Member"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PlanNameDomain_721f84af-c676-472c-99bb-4c5a14225440" xlink:to="loc_espr_StockOptionAndIncentivePlan2022Member_94d73515-eb38-49b0-96a3-769ed90f9a00" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_InducementEquityPlan2017Member_098c085f-6244-49af-ac63-089651007b7c" xlink:href="espr-20240331.xsd#espr_InducementEquityPlan2017Member"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PlanNameDomain_721f84af-c676-472c-99bb-4c5a14225440" xlink:to="loc_espr_InducementEquityPlan2017Member_098c085f-6244-49af-ac63-089651007b7c" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAuthorized_4df42d26-7dfa-4bc5-9f5d-afa23d1e9e92" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAuthorized"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_7770403c-ad11-4e91-903f-347944712685" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAuthorized_4df42d26-7dfa-4bc5-9f5d-afa23d1e9e92" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_EmployeeStockPurchasePlanMaximumAnnualContributionsPerEmployeePercent_2e9244cd-896c-4396-a960-51421ac9ffa2" xlink:href="espr-20240331.xsd#espr_EmployeeStockPurchasePlanMaximumAnnualContributionsPerEmployeePercent"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_7770403c-ad11-4e91-903f-347944712685" xlink:to="loc_espr_EmployeeStockPurchasePlanMaximumAnnualContributionsPerEmployeePercent_2e9244cd-896c-4396-a960-51421ac9ffa2" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_EmployeeStockPurchasePlanMaximumAnnualContributionsPerEmployeeAmount_d5500227-041f-4768-9304-a7440ddf45a9" xlink:href="espr-20240331.xsd#espr_EmployeeStockPurchasePlanMaximumAnnualContributionsPerEmployeeAmount"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_7770403c-ad11-4e91-903f-347944712685" xlink:to="loc_espr_EmployeeStockPurchasePlanMaximumAnnualContributionsPerEmployeeAmount_d5500227-041f-4768-9304-a7440ddf45a9" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_EmployeeStockPurchasePlanPercentageDiscountOnShares_cb2ab33f-82a3-42a7-918a-7937ce9dcf1e" xlink:href="espr-20240331.xsd#espr_EmployeeStockPurchasePlanPercentageDiscountOnShares"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_7770403c-ad11-4e91-903f-347944712685" xlink:to="loc_espr_EmployeeStockPurchasePlanPercentageDiscountOnShares_cb2ab33f-82a3-42a7-918a-7937ce9dcf1e" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_EmployeeStockPurchasePlanDurationOfOfferingPeriod_0324f24c-7f55-4864-ab4e-bcc4d12dfe31" xlink:href="espr-20240331.xsd#espr_EmployeeStockPurchasePlanDurationOfOfferingPeriod"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_7770403c-ad11-4e91-903f-347944712685" xlink:to="loc_espr_EmployeeStockPurchasePlanDurationOfOfferingPeriod_0324f24c-7f55-4864-ab4e-bcc4d12dfe31" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AllocatedShareBasedCompensationExpense_52595631-4580-4d8d-ba04-5512ac2253f3" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_AllocatedShareBasedCompensationExpense"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_7770403c-ad11-4e91-903f-347944712685" xlink:to="loc_us-gaap_AllocatedShareBasedCompensationExpense_52595631-4580-4d8d-ba04-5512ac2253f3" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardSharesIssuedInPeriod_2db6a38b-6092-4aab-8ac6-974f66f924e4" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardSharesIssuedInPeriod"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_7770403c-ad11-4e91-903f-347944712685" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardSharesIssuedInPeriod_2db6a38b-6092-4aab-8ac6-974f66f924e4" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CommonStockCapitalSharesReservedForFutureIssuance_eac82a7c-8b38-4620-ac1c-01b9c4c78760" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_CommonStockCapitalSharesReservedForFutureIssuance"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_7770403c-ad11-4e91-903f-347944712685" xlink:to="loc_us-gaap_CommonStockCapitalSharesReservedForFutureIssuance_eac82a7c-8b38-4620-ac1c-01b9c4c78760" xlink:type="arc" order="7"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsCapitalizedAmount_ece5a085-3425-42f2-aec1-f4a88571c566" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_EmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsCapitalizedAmount"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_7770403c-ad11-4e91-903f-347944712685" xlink:to="loc_us-gaap_EmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsCapitalizedAmount_ece5a085-3425-42f2-aec1-f4a88571c566" xlink:type="arc" order="8"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedStockOptions_547e7224-66fe-4f33-9fe8-9475f8622384" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedStockOptions"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_7770403c-ad11-4e91-903f-347944712685" xlink:to="loc_us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedStockOptions_547e7224-66fe-4f33-9fe8-9475f8622384" xlink:type="arc" order="9"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1_1803ab87-5812-43ce-aa6e-e54d18cd7517" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_7770403c-ad11-4e91-903f-347944712685" xlink:to="loc_us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1_1803ab87-5812-43ce-aa6e-e54d18cd7517" xlink:type="arc" order="10"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.esperion.com/role/StockCompensationPBSOsDetails" xlink:type="simple" xlink:href="espr-20240331.xsd#StockCompensationPBSOsDetails"/>
  <link:definitionLink xlink:role="http://www.esperion.com/role/StockCompensationPBSOsDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_74c6cccd-5499-47d7-af02-7dd34ce49e5b" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_3c8842f8-5e10-487f-9977-e12319bd97d0" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_74c6cccd-5499-47d7-af02-7dd34ce49e5b" xlink:to="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_3c8842f8-5e10-487f-9977-e12319bd97d0" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AwardTypeAxis_e47ab5e2-865a-45ac-8ddc-8752c4e35ec8" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_AwardTypeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_3c8842f8-5e10-487f-9977-e12319bd97d0" xlink:to="loc_us-gaap_AwardTypeAxis_e47ab5e2-865a-45ac-8ddc-8752c4e35ec8" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_e47ab5e2-865a-45ac-8ddc-8752c4e35ec8_default" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_AwardTypeAxis_e47ab5e2-865a-45ac-8ddc-8752c4e35ec8" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_e47ab5e2-865a-45ac-8ddc-8752c4e35ec8_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_520ef631-ae95-4ee1-b11c-7ab856b4ee09" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_AwardTypeAxis_e47ab5e2-865a-45ac-8ddc-8752c4e35ec8" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_520ef631-ae95-4ee1-b11c-7ab856b4ee09" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_ShareBasedPaymentArrangementOptionPerformanceBasedMember_1559e807-cda1-46c5-8e7a-aefe1feb3284" xlink:href="espr-20240331.xsd#espr_ShareBasedPaymentArrangementOptionPerformanceBasedMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_520ef631-ae95-4ee1-b11c-7ab856b4ee09" xlink:to="loc_espr_ShareBasedPaymentArrangementOptionPerformanceBasedMember_1559e807-cda1-46c5-8e7a-aefe1feb3284" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingRollForward_bbf54ed0-378e-44a1-adce-6bd063f483c8" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingRollForward"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_74c6cccd-5499-47d7-af02-7dd34ce49e5b" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingRollForward_bbf54ed0-378e-44a1-adce-6bd063f483c8" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingNumber_bc1f1b05-894b-48db-ad1e-9ed160a5aa78" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingNumber"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingRollForward_bbf54ed0-378e-44a1-adce-6bd063f483c8" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingNumber_bc1f1b05-894b-48db-ad1e-9ed160a5aa78" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsGrantsInPeriodGross_38a6f229-39be-49aa-9dcf-310a3d0c9c10" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsGrantsInPeriodGross"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingRollForward_bbf54ed0-378e-44a1-adce-6bd063f483c8" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsGrantsInPeriodGross_38a6f229-39be-49aa-9dcf-310a3d0c9c10" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsForfeituresAndExpirationsInPeriod_2dba4ed5-9731-4e6b-be3f-7f3fa700e7ff" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsForfeituresAndExpirationsInPeriod"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingRollForward_bbf54ed0-378e-44a1-adce-6bd063f483c8" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsForfeituresAndExpirationsInPeriod_2dba4ed5-9731-4e6b-be3f-7f3fa700e7ff" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StockIssuedDuringPeriodSharesStockOptionsExercised_9c06bf99-ff18-40a1-8f61-4ff7048075d2" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_StockIssuedDuringPeriodSharesStockOptionsExercised"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingRollForward_bbf54ed0-378e-44a1-adce-6bd063f483c8" xlink:to="loc_us-gaap_StockIssuedDuringPeriodSharesStockOptionsExercised_9c06bf99-ff18-40a1-8f61-4ff7048075d2" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingNumber_35868c5a-feb4-431b-b28d-f982ec092c17" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingNumber"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsVestedAndExpectedToVestOutstandingNumber_e8ed89fe-617c-4c33-937c-218e90b45dc2" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsVestedAndExpectedToVestOutstandingNumber"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_74c6cccd-5499-47d7-af02-7dd34ce49e5b" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsVestedAndExpectedToVestOutstandingNumber_e8ed89fe-617c-4c33-937c-218e90b45dc2" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsExercisableNumber_41431b0e-4214-42c6-9ebe-bf1b5b52fd58" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsExercisableNumber"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_74c6cccd-5499-47d7-af02-7dd34ce49e5b" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsExercisableNumber_41431b0e-4214-42c6-9ebe-bf1b5b52fd58" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingWeightedAverageExercisePriceRollforward_bcdc15ce-fc30-400f-8d79-44ba1d8193fe" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingWeightedAverageExercisePriceRollforward"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_74c6cccd-5499-47d7-af02-7dd34ce49e5b" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingWeightedAverageExercisePriceRollforward_bcdc15ce-fc30-400f-8d79-44ba1d8193fe" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingWeightedAverageExercisePrice_bb610f5f-88df-44e4-8542-70b8f7ffeef8" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingWeightedAverageExercisePrice"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingWeightedAverageExercisePriceRollforward_bcdc15ce-fc30-400f-8d79-44ba1d8193fe" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingWeightedAverageExercisePrice_bb610f5f-88df-44e4-8542-70b8f7ffeef8" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardOptionsGrantsInPeriodWeightedAverageExercisePrice_ab3420fb-1eaf-488e-b3a7-699050d05ee1" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardOptionsGrantsInPeriodWeightedAverageExercisePrice"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingWeightedAverageExercisePriceRollforward_bcdc15ce-fc30-400f-8d79-44ba1d8193fe" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardOptionsGrantsInPeriodWeightedAverageExercisePrice_ab3420fb-1eaf-488e-b3a7-699050d05ee1" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsForfeituresAndExpirationsInPeriodWeightedAverageExercisePrice_9f04c46c-312b-4b73-901b-f4a71e712d7b" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsForfeituresAndExpirationsInPeriodWeightedAverageExercisePrice"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingWeightedAverageExercisePriceRollforward_bcdc15ce-fc30-400f-8d79-44ba1d8193fe" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsForfeituresAndExpirationsInPeriodWeightedAverageExercisePrice_9f04c46c-312b-4b73-901b-f4a71e712d7b" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardOptionsExercisesInPeriodWeightedAverageExercisePrice_e42f77bf-eda2-42f3-b142-2e1e10b3d776" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardOptionsExercisesInPeriodWeightedAverageExercisePrice"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingWeightedAverageExercisePriceRollforward_bcdc15ce-fc30-400f-8d79-44ba1d8193fe" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardOptionsExercisesInPeriodWeightedAverageExercisePrice_e42f77bf-eda2-42f3-b142-2e1e10b3d776" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingWeightedAverageExercisePrice_b178db52-8059-487c-a2cf-7e0f98ede7b1" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingWeightedAverageExercisePrice"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsVestedAndExpectedToVestOutstandingWeightedAverageExercisePrice_e5bd9e58-7658-4021-853d-e66d9d4c583e" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsVestedAndExpectedToVestOutstandingWeightedAverageExercisePrice"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_74c6cccd-5499-47d7-af02-7dd34ce49e5b" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsVestedAndExpectedToVestOutstandingWeightedAverageExercisePrice_e5bd9e58-7658-4021-853d-e66d9d4c583e" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsExercisableWeightedAverageExercisePrice_47fdb9fe-a2c4-4b9a-a08f-a9fc29aef06c" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsExercisableWeightedAverageExercisePrice"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_74c6cccd-5499-47d7-af02-7dd34ce49e5b" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsExercisableWeightedAverageExercisePrice_47fdb9fe-a2c4-4b9a-a08f-a9fc29aef06c" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsWeightedAverageRemainingContractualTermAbstract_27b2d2ef-cfe5-4ddc-b34c-09edf992573d" xlink:href="espr-20240331.xsd#espr_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsWeightedAverageRemainingContractualTermAbstract"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_74c6cccd-5499-47d7-af02-7dd34ce49e5b" xlink:to="loc_espr_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsWeightedAverageRemainingContractualTermAbstract_27b2d2ef-cfe5-4ddc-b34c-09edf992573d" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardOptionsOutstandingWeightedAverageRemainingContractualTerm2_ea8f7d8f-8c61-4537-b1d5-3de5cbcda219" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardOptionsOutstandingWeightedAverageRemainingContractualTerm2"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_espr_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsWeightedAverageRemainingContractualTermAbstract_27b2d2ef-cfe5-4ddc-b34c-09edf992573d" xlink:to="loc_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardOptionsOutstandingWeightedAverageRemainingContractualTerm2_ea8f7d8f-8c61-4537-b1d5-3de5cbcda219" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardOptionsVestedAndExpectedToVestOutstandingWeightedAverageRemainingContractualTerm1_a2acd8d3-d868-4263-9202-0f4d437562b9" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardOptionsVestedAndExpectedToVestOutstandingWeightedAverageRemainingContractualTerm1"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_espr_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsWeightedAverageRemainingContractualTermAbstract_27b2d2ef-cfe5-4ddc-b34c-09edf992573d" xlink:to="loc_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardOptionsVestedAndExpectedToVestOutstandingWeightedAverageRemainingContractualTerm1_a2acd8d3-d868-4263-9202-0f4d437562b9" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardOptionsExercisableWeightedAverageRemainingContractualTerm1_ab364b5a-53d5-447c-9f6b-1ad495eb4cf1" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardOptionsExercisableWeightedAverageRemainingContractualTerm1"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_espr_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsWeightedAverageRemainingContractualTermAbstract_27b2d2ef-cfe5-4ddc-b34c-09edf992573d" xlink:to="loc_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardOptionsExercisableWeightedAverageRemainingContractualTerm1_ab364b5a-53d5-447c-9f6b-1ad495eb4cf1" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_ShareBasedCompensationArrangementByShareBasedPaymentAwardAggregateIntrinsicValueAbstract_fc4fa80f-bd9c-445a-99d5-b850660c674b" xlink:href="espr-20240331.xsd#espr_ShareBasedCompensationArrangementByShareBasedPaymentAwardAggregateIntrinsicValueAbstract"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_74c6cccd-5499-47d7-af02-7dd34ce49e5b" xlink:to="loc_espr_ShareBasedCompensationArrangementByShareBasedPaymentAwardAggregateIntrinsicValueAbstract_fc4fa80f-bd9c-445a-99d5-b850660c674b" xlink:type="arc" order="7"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingIntrinsicValue_796c1b81-fb73-4943-9ef0-92b28e180044" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingIntrinsicValue"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_espr_ShareBasedCompensationArrangementByShareBasedPaymentAwardAggregateIntrinsicValueAbstract_fc4fa80f-bd9c-445a-99d5-b850660c674b" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingIntrinsicValue_796c1b81-fb73-4943-9ef0-92b28e180044" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsVestedAndExpectedToVestOutstandingAggregateIntrinsicValue_54b4a61e-4800-4676-ad96-2e13deb3daf8" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsVestedAndExpectedToVestOutstandingAggregateIntrinsicValue"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_espr_ShareBasedCompensationArrangementByShareBasedPaymentAwardAggregateIntrinsicValueAbstract_fc4fa80f-bd9c-445a-99d5-b850660c674b" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsVestedAndExpectedToVestOutstandingAggregateIntrinsicValue_54b4a61e-4800-4676-ad96-2e13deb3daf8" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardOptionsExercisableIntrinsicValue1_2eda30fe-b01a-4747-bfaa-813925b46a9e" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardOptionsExercisableIntrinsicValue1"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_espr_ShareBasedCompensationArrangementByShareBasedPaymentAwardAggregateIntrinsicValueAbstract_fc4fa80f-bd9c-445a-99d5-b850660c674b" xlink:to="loc_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardOptionsExercisableIntrinsicValue1_2eda30fe-b01a-4747-bfaa-813925b46a9e" xlink:type="arc" order="3"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.esperion.com/role/StockCompensationRSUsDetails" xlink:type="simple" xlink:href="espr-20240331.xsd#StockCompensationRSUsDetails"/>
  <link:definitionLink xlink:role="http://www.esperion.com/role/StockCompensationRSUsDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_5b95bb72-f348-4d37-9b71-c3d2558fe27c" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_b894f60b-95b1-497c-8b0b-bbd07056443e" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_5b95bb72-f348-4d37-9b71-c3d2558fe27c" xlink:to="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_b894f60b-95b1-497c-8b0b-bbd07056443e" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AwardTypeAxis_f37c21c1-4e4c-4d96-b05f-787196e6c707" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_AwardTypeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_b894f60b-95b1-497c-8b0b-bbd07056443e" xlink:to="loc_us-gaap_AwardTypeAxis_f37c21c1-4e4c-4d96-b05f-787196e6c707" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_f37c21c1-4e4c-4d96-b05f-787196e6c707_default" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_AwardTypeAxis_f37c21c1-4e4c-4d96-b05f-787196e6c707" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_f37c21c1-4e4c-4d96-b05f-787196e6c707_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_b18004c3-97df-43b4-ae1f-0ce8f77df72c" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_AwardTypeAxis_f37c21c1-4e4c-4d96-b05f-787196e6c707" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_b18004c3-97df-43b4-ae1f-0ce8f77df72c" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RestrictedStockUnitsRSUMember_c5fd371a-bc69-476d-87a6-f05833e953e2" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_RestrictedStockUnitsRSUMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_b18004c3-97df-43b4-ae1f-0ce8f77df72c" xlink:to="loc_us-gaap_RestrictedStockUnitsRSUMember_c5fd371a-bc69-476d-87a6-f05833e953e2" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedRollForward_bece2df8-e04f-4ee8-866f-bdb07e668541" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedRollForward"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_5b95bb72-f348-4d37-9b71-c3d2558fe27c" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedRollForward_bece2df8-e04f-4ee8-866f-bdb07e668541" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedNumber_f4c37c57-4a05-4df7-a4ce-091dae12e7bf" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedNumber"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedRollForward_bece2df8-e04f-4ee8-866f-bdb07e668541" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedNumber_f4c37c57-4a05-4df7-a4ce-091dae12e7bf" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsGrantsInPeriod_78e7d31b-6776-4c3a-a928-c2422ea7b8d7" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsGrantsInPeriod"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedRollForward_bece2df8-e04f-4ee8-866f-bdb07e668541" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsGrantsInPeriod_78e7d31b-6776-4c3a-a928-c2422ea7b8d7" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsForfeitedInPeriod_89e76f87-5498-4ced-9bab-908631510ac4" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsForfeitedInPeriod"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedRollForward_bece2df8-e04f-4ee8-866f-bdb07e668541" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsForfeitedInPeriod_89e76f87-5498-4ced-9bab-908631510ac4" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsVestedInPeriod_07d2a1a5-4e38-4bdf-b0a1-e9ba35cdb77b" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsVestedInPeriod"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedRollForward_bece2df8-e04f-4ee8-866f-bdb07e668541" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsVestedInPeriod_07d2a1a5-4e38-4bdf-b0a1-e9ba35cdb77b" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedNumber_2c776850-6b89-4210-acd6-7c553ca7de5d" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedNumber"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValueRollForward_812a6842-7210-4557-bfc9-c7ddc976d8af" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValueRollForward"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_5b95bb72-f348-4d37-9b71-c3d2558fe27c" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValueRollForward_812a6842-7210-4557-bfc9-c7ddc976d8af" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValue_ce062926-cd98-4895-9784-048516600e0b" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValue"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValueRollForward_812a6842-7210-4557-bfc9-c7ddc976d8af" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValue_ce062926-cd98-4895-9784-048516600e0b" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsGrantsInPeriodWeightedAverageGrantDateFairValue_a74c0b7a-1aa8-4962-9715-fd9fb827b9ad" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsGrantsInPeriodWeightedAverageGrantDateFairValue"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValueRollForward_812a6842-7210-4557-bfc9-c7ddc976d8af" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsGrantsInPeriodWeightedAverageGrantDateFairValue_a74c0b7a-1aa8-4962-9715-fd9fb827b9ad" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsForfeituresWeightedAverageGrantDateFairValue_5b81523e-f78a-4f25-be01-8d261de5b935" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsForfeituresWeightedAverageGrantDateFairValue"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValueRollForward_812a6842-7210-4557-bfc9-c7ddc976d8af" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsForfeituresWeightedAverageGrantDateFairValue_5b81523e-f78a-4f25-be01-8d261de5b935" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsVestedInPeriodWeightedAverageGrantDateFairValue_a4d8b674-135b-46dc-ae4a-719f855b7fa4" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsVestedInPeriodWeightedAverageGrantDateFairValue"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValueRollForward_812a6842-7210-4557-bfc9-c7ddc976d8af" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsVestedInPeriodWeightedAverageGrantDateFairValue_a4d8b674-135b-46dc-ae4a-719f855b7fa4" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValue_7db3c574-17a4-4357-9edd-112f5375d044" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValue"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.esperion.com/role/StockCompensationPBRSUsDetails" xlink:type="simple" xlink:href="espr-20240331.xsd#StockCompensationPBRSUsDetails"/>
  <link:definitionLink xlink:role="http://www.esperion.com/role/StockCompensationPBRSUsDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_b28b620b-d014-49fe-9cf4-3f9ac338f25f" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_04aa2364-4748-4675-834b-2f6f919aa8cd" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_b28b620b-d014-49fe-9cf4-3f9ac338f25f" xlink:to="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_04aa2364-4748-4675-834b-2f6f919aa8cd" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AwardTypeAxis_6db19370-bdb3-4c96-9f66-dc71e7739b24" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_AwardTypeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_04aa2364-4748-4675-834b-2f6f919aa8cd" xlink:to="loc_us-gaap_AwardTypeAxis_6db19370-bdb3-4c96-9f66-dc71e7739b24" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_6db19370-bdb3-4c96-9f66-dc71e7739b24_default" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_AwardTypeAxis_6db19370-bdb3-4c96-9f66-dc71e7739b24" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_6db19370-bdb3-4c96-9f66-dc71e7739b24_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_877187eb-ede4-49e1-adf2-beeeebca391c" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_AwardTypeAxis_6db19370-bdb3-4c96-9f66-dc71e7739b24" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_877187eb-ede4-49e1-adf2-beeeebca391c" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PerformanceSharesMember_a2a14716-9161-4542-a0e9-4d35354d8055" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_PerformanceSharesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_877187eb-ede4-49e1-adf2-beeeebca391c" xlink:to="loc_us-gaap_PerformanceSharesMember_a2a14716-9161-4542-a0e9-4d35354d8055" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedRollForward_78d56c18-4157-4c2e-8e99-6bbe9ed04e6c" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedRollForward"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_b28b620b-d014-49fe-9cf4-3f9ac338f25f" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedRollForward_78d56c18-4157-4c2e-8e99-6bbe9ed04e6c" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedNumber_d0ac1121-fb2b-4809-873e-e5eb0cf841f4" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedNumber"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedRollForward_78d56c18-4157-4c2e-8e99-6bbe9ed04e6c" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedNumber_d0ac1121-fb2b-4809-873e-e5eb0cf841f4" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsGrantsInPeriod_97113302-075d-4dc3-afa3-9ee21c811e41" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsGrantsInPeriod"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedRollForward_78d56c18-4157-4c2e-8e99-6bbe9ed04e6c" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsGrantsInPeriod_97113302-075d-4dc3-afa3-9ee21c811e41" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsForfeitedInPeriod_336d257b-dd3c-4222-afb9-131be406582f" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsForfeitedInPeriod"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedRollForward_78d56c18-4157-4c2e-8e99-6bbe9ed04e6c" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsForfeitedInPeriod_336d257b-dd3c-4222-afb9-131be406582f" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsVestedInPeriod_dfc4b173-13cc-42a1-8466-3c98cdb80d8b" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsVestedInPeriod"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedRollForward_78d56c18-4157-4c2e-8e99-6bbe9ed04e6c" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsVestedInPeriod_dfc4b173-13cc-42a1-8466-3c98cdb80d8b" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedNumber_4b298534-6f9a-4384-814d-2b5b0de6e9dd" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedNumber"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValueRollForward_48dcd2ea-f0f2-4bb8-8134-a9886f7b8e7c" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValueRollForward"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_b28b620b-d014-49fe-9cf4-3f9ac338f25f" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValueRollForward_48dcd2ea-f0f2-4bb8-8134-a9886f7b8e7c" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValue_40cd2f94-de0a-48bc-8cfa-1dddb2fd77ef" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValue"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValueRollForward_48dcd2ea-f0f2-4bb8-8134-a9886f7b8e7c" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValue_40cd2f94-de0a-48bc-8cfa-1dddb2fd77ef" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsGrantsInPeriodWeightedAverageGrantDateFairValue_55e41ad7-964a-4571-8e0c-89e25fdc64bc" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsGrantsInPeriodWeightedAverageGrantDateFairValue"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValueRollForward_48dcd2ea-f0f2-4bb8-8134-a9886f7b8e7c" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsGrantsInPeriodWeightedAverageGrantDateFairValue_55e41ad7-964a-4571-8e0c-89e25fdc64bc" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsForfeituresWeightedAverageGrantDateFairValue_cf5d67e8-89be-4d0b-9f23-ddddb3768795" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsForfeituresWeightedAverageGrantDateFairValue"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValueRollForward_48dcd2ea-f0f2-4bb8-8134-a9886f7b8e7c" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsForfeituresWeightedAverageGrantDateFairValue_cf5d67e8-89be-4d0b-9f23-ddddb3768795" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsVestedInPeriodWeightedAverageGrantDateFairValue_904e6f2d-2433-4320-b7a3-987a43d0d227" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsVestedInPeriodWeightedAverageGrantDateFairValue"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValueRollForward_48dcd2ea-f0f2-4bb8-8134-a9886f7b8e7c" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsVestedInPeriodWeightedAverageGrantDateFairValue_904e6f2d-2433-4320-b7a3-987a43d0d227" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValue_e6dee742-31cc-4490-a8aa-a5d76450b42a" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValue"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.esperion.com/role/StockholdersDeficitDetails" xlink:type="simple" xlink:href="espr-20240331.xsd#StockholdersDeficitDetails"/>
  <link:definitionLink xlink:role="http://www.esperion.com/role/StockholdersDeficitDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SubsidiarySaleOfStockLineItems_9af128fa-eb08-45bf-8e9c-a104fe36d96c" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_SubsidiarySaleOfStockLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SubsidiaryOrEquityMethodInvesteeSaleOfStockBySubsidiaryOrEquityInvesteeTable_894600af-c2b0-4ae2-8211-09872d61396b" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_SubsidiaryOrEquityMethodInvesteeSaleOfStockBySubsidiaryOrEquityInvesteeTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_SubsidiarySaleOfStockLineItems_9af128fa-eb08-45bf-8e9c-a104fe36d96c" xlink:to="loc_us-gaap_SubsidiaryOrEquityMethodInvesteeSaleOfStockBySubsidiaryOrEquityInvesteeTable_894600af-c2b0-4ae2-8211-09872d61396b" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SubsidiarySaleOfStockAxis_be11e272-066a-419f-8091-cb504aa31508" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_SubsidiarySaleOfStockAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_SubsidiaryOrEquityMethodInvesteeSaleOfStockBySubsidiaryOrEquityInvesteeTable_894600af-c2b0-4ae2-8211-09872d61396b" xlink:to="loc_us-gaap_SubsidiarySaleOfStockAxis_be11e272-066a-419f-8091-cb504aa31508" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SaleOfStockNameOfTransactionDomain_be11e272-066a-419f-8091-cb504aa31508_default" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_SaleOfStockNameOfTransactionDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_SubsidiarySaleOfStockAxis_be11e272-066a-419f-8091-cb504aa31508" xlink:to="loc_us-gaap_SaleOfStockNameOfTransactionDomain_be11e272-066a-419f-8091-cb504aa31508_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SaleOfStockNameOfTransactionDomain_8849b060-ff00-4202-a2ca-fce37dcc0e8a" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_SaleOfStockNameOfTransactionDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_SubsidiarySaleOfStockAxis_be11e272-066a-419f-8091-cb504aa31508" xlink:to="loc_us-gaap_SaleOfStockNameOfTransactionDomain_8849b060-ff00-4202-a2ca-fce37dcc0e8a" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_CommitmentOfferingMember_daa040d8-1147-4d96-9a99-ebfd4badc971" xlink:href="espr-20240331.xsd#espr_CommitmentOfferingMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SaleOfStockNameOfTransactionDomain_8849b060-ff00-4202-a2ca-fce37dcc0e8a" xlink:to="loc_espr_CommitmentOfferingMember_daa040d8-1147-4d96-9a99-ebfd4badc971" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OverAllotmentOptionMember_5f7ca0be-826d-47bf-ad7e-2f24fabec293" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_OverAllotmentOptionMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SaleOfStockNameOfTransactionDomain_8849b060-ff00-4202-a2ca-fce37dcc0e8a" xlink:to="loc_us-gaap_OverAllotmentOptionMember_5f7ca0be-826d-47bf-ad7e-2f24fabec293" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_AtTheMarketProgramMember_d8226796-1fdf-4ba5-90e7-6a950e6ccd8d" xlink:href="espr-20240331.xsd#espr_AtTheMarketProgramMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SaleOfStockNameOfTransactionDomain_8849b060-ff00-4202-a2ca-fce37dcc0e8a" xlink:to="loc_espr_AtTheMarketProgramMember_d8226796-1fdf-4ba5-90e7-6a950e6ccd8d" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_TypeOfArrangementAxis_fb5f5a7a-aacc-4eda-869d-f340abc2028e" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_TypeOfArrangementAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_SubsidiaryOrEquityMethodInvesteeSaleOfStockBySubsidiaryOrEquityInvesteeTable_894600af-c2b0-4ae2-8211-09872d61396b" xlink:to="loc_us-gaap_TypeOfArrangementAxis_fb5f5a7a-aacc-4eda-869d-f340abc2028e" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ArrangementsAndNonarrangementTransactionsMember_fb5f5a7a-aacc-4eda-869d-f340abc2028e_default" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ArrangementsAndNonarrangementTransactionsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_TypeOfArrangementAxis_fb5f5a7a-aacc-4eda-869d-f340abc2028e" xlink:to="loc_us-gaap_ArrangementsAndNonarrangementTransactionsMember_fb5f5a7a-aacc-4eda-869d-f340abc2028e_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ArrangementsAndNonarrangementTransactionsMember_4eba63a2-09ca-4e3a-b91e-609a3664d2f0" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ArrangementsAndNonarrangementTransactionsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_TypeOfArrangementAxis_fb5f5a7a-aacc-4eda-869d-f340abc2028e" xlink:to="loc_us-gaap_ArrangementsAndNonarrangementTransactionsMember_4eba63a2-09ca-4e3a-b91e-609a3664d2f0" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_WainwrightMember_31eed89b-e8b2-49c0-a2fb-fa21888af2be" xlink:href="espr-20240331.xsd#espr_WainwrightMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ArrangementsAndNonarrangementTransactionsMember_4eba63a2-09ca-4e3a-b91e-609a3664d2f0" xlink:to="loc_espr_WainwrightMember_31eed89b-e8b2-49c0-a2fb-fa21888af2be" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_WarrantAmendmentAgreementsMember_5c0a922c-e5f5-403d-9457-f2feea635816" xlink:href="espr-20240331.xsd#espr_WarrantAmendmentAgreementsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ArrangementsAndNonarrangementTransactionsMember_4eba63a2-09ca-4e3a-b91e-609a3664d2f0" xlink:to="loc_espr_WarrantAmendmentAgreementsMember_5c0a922c-e5f5-403d-9457-f2feea635816" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_SecuritiesPurchaseAgreementMember_8b3e15b0-eb3c-4505-8da9-b0c13bcac7bd" xlink:href="espr-20240331.xsd#espr_SecuritiesPurchaseAgreementMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ArrangementsAndNonarrangementTransactionsMember_4eba63a2-09ca-4e3a-b91e-609a3664d2f0" xlink:to="loc_espr_SecuritiesPurchaseAgreementMember_8b3e15b0-eb3c-4505-8da9-b0c13bcac7bd" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ClassOfWarrantOrRightAxis_2c3d136f-0ed5-40df-ab48-343e1a771087" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ClassOfWarrantOrRightAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_SubsidiaryOrEquityMethodInvesteeSaleOfStockBySubsidiaryOrEquityInvesteeTable_894600af-c2b0-4ae2-8211-09872d61396b" xlink:to="loc_us-gaap_ClassOfWarrantOrRightAxis_2c3d136f-0ed5-40df-ab48-343e1a771087" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ClassOfWarrantOrRightDomain_2c3d136f-0ed5-40df-ab48-343e1a771087_default" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ClassOfWarrantOrRightDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_ClassOfWarrantOrRightAxis_2c3d136f-0ed5-40df-ab48-343e1a771087" xlink:to="loc_us-gaap_ClassOfWarrantOrRightDomain_2c3d136f-0ed5-40df-ab48-343e1a771087_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ClassOfWarrantOrRightDomain_5a77fb26-8575-4712-89af-b83e45eadac9" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ClassOfWarrantOrRightDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_ClassOfWarrantOrRightAxis_2c3d136f-0ed5-40df-ab48-343e1a771087" xlink:to="loc_us-gaap_ClassOfWarrantOrRightDomain_5a77fb26-8575-4712-89af-b83e45eadac9" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_CommonStockAndAccompanyingWarrantMember_11eeb0e8-78d7-46ac-8cd8-3ea3c24aaca0" xlink:href="espr-20240331.xsd#espr_CommonStockAndAccompanyingWarrantMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfWarrantOrRightDomain_5a77fb26-8575-4712-89af-b83e45eadac9" xlink:to="loc_espr_CommonStockAndAccompanyingWarrantMember_11eeb0e8-78d7-46ac-8cd8-3ea3c24aaca0" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_TheWarrantsMember_95f5f7f3-477a-4ccc-b276-b77c130249a7" xlink:href="espr-20240331.xsd#espr_TheWarrantsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfWarrantOrRightDomain_5a77fb26-8575-4712-89af-b83e45eadac9" xlink:to="loc_espr_TheWarrantsMember_95f5f7f3-477a-4ccc-b276-b77c130249a7" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_PreFundedWarrantAndAccompanyingWarrantMember_4410db57-6648-45ac-b3a6-b011a30c60c1" xlink:href="espr-20240331.xsd#espr_PreFundedWarrantAndAccompanyingWarrantMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfWarrantOrRightDomain_5a77fb26-8575-4712-89af-b83e45eadac9" xlink:to="loc_espr_PreFundedWarrantAndAccompanyingWarrantMember_4410db57-6648-45ac-b3a6-b011a30c60c1" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_PreFundedWarrantMember_dd951c02-52f9-466f-b5bb-230c397d8fbd" xlink:href="espr-20240331.xsd#espr_PreFundedWarrantMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfWarrantOrRightDomain_5a77fb26-8575-4712-89af-b83e45eadac9" xlink:to="loc_espr_PreFundedWarrantMember_dd951c02-52f9-466f-b5bb-230c397d8fbd" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_WarrantsMember_edcdb27e-4c66-49e1-a3e4-78d5fd9ccfde" xlink:href="espr-20240331.xsd#espr_WarrantsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfWarrantOrRightDomain_5a77fb26-8575-4712-89af-b83e45eadac9" xlink:to="loc_espr_WarrantsMember_edcdb27e-4c66-49e1-a3e4-78d5fd9ccfde" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SaleOfStockNumberOfSharesIssuedInTransaction_b2644c63-5756-4241-b2c4-dfdd65d62d92" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_SaleOfStockNumberOfSharesIssuedInTransaction"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SubsidiarySaleOfStockLineItems_9af128fa-eb08-45bf-8e9c-a104fe36d96c" xlink:to="loc_us-gaap_SaleOfStockNumberOfSharesIssuedInTransaction_b2644c63-5756-4241-b2c4-dfdd65d62d92" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SaleOfStockPricePerShare_1a585b24-23b7-42fb-b38d-324c332e4437" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_SaleOfStockPricePerShare"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SubsidiarySaleOfStockLineItems_9af128fa-eb08-45bf-8e9c-a104fe36d96c" xlink:to="loc_us-gaap_SaleOfStockPricePerShare_1a585b24-23b7-42fb-b38d-324c332e4437" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_SaleOfStockUnderwriterOptionPeriod_6d9f952f-c665-4fb7-9ee2-76a684187e93" xlink:href="espr-20240331.xsd#espr_SaleOfStockUnderwriterOptionPeriod"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SubsidiarySaleOfStockLineItems_9af128fa-eb08-45bf-8e9c-a104fe36d96c" xlink:to="loc_espr_SaleOfStockUnderwriterOptionPeriod_6d9f952f-c665-4fb7-9ee2-76a684187e93" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SaleOfStockConsiderationReceivedOnTransaction_e419b715-ac0d-4377-8f8b-8fdac2402e82" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_SaleOfStockConsiderationReceivedOnTransaction"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SubsidiarySaleOfStockLineItems_9af128fa-eb08-45bf-8e9c-a104fe36d96c" xlink:to="loc_us-gaap_SaleOfStockConsiderationReceivedOnTransaction_e419b715-ac0d-4377-8f8b-8fdac2402e82" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PaymentsForCommissions_e43ec57c-472d-48ff-9758-53771470b70f" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_PaymentsForCommissions"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SubsidiarySaleOfStockLineItems_9af128fa-eb08-45bf-8e9c-a104fe36d96c" xlink:to="loc_us-gaap_PaymentsForCommissions_e43ec57c-472d-48ff-9758-53771470b70f" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_SaleOfStockAuthorizedAmount_afbc5714-6ecf-44c7-a354-53d7f1ae60f7" xlink:href="espr-20240331.xsd#espr_SaleOfStockAuthorizedAmount"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SubsidiarySaleOfStockLineItems_9af128fa-eb08-45bf-8e9c-a104fe36d96c" xlink:to="loc_espr_SaleOfStockAuthorizedAmount_afbc5714-6ecf-44c7-a354-53d7f1ae60f7" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PaymentsOfStockIssuanceCosts_3ed6e87d-dbee-4c4a-9941-8dce6304a1fd" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_PaymentsOfStockIssuanceCosts"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SubsidiarySaleOfStockLineItems_9af128fa-eb08-45bf-8e9c-a104fe36d96c" xlink:to="loc_us-gaap_PaymentsOfStockIssuanceCosts_3ed6e87d-dbee-4c4a-9941-8dce6304a1fd" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ClassOfWarrantOrRightOutstanding_d0ec8f24-626e-401a-adcd-8e9cc699883e" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ClassOfWarrantOrRightOutstanding"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SubsidiarySaleOfStockLineItems_9af128fa-eb08-45bf-8e9c-a104fe36d96c" xlink:to="loc_us-gaap_ClassOfWarrantOrRightOutstanding_d0ec8f24-626e-401a-adcd-8e9cc699883e" xlink:type="arc" order="7"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ClassOfWarrantOrRightExercisePriceOfWarrantsOrRights1_875cdc1a-599b-4305-8d6f-d7762a74b427" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ClassOfWarrantOrRightExercisePriceOfWarrantsOrRights1"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SubsidiarySaleOfStockLineItems_9af128fa-eb08-45bf-8e9c-a104fe36d96c" xlink:to="loc_us-gaap_ClassOfWarrantOrRightExercisePriceOfWarrantsOrRights1_875cdc1a-599b-4305-8d6f-d7762a74b427" xlink:type="arc" order="8"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AdjustmentsToAdditionalPaidInCapitalWarrantIssued_328f7984-e132-47fb-b791-90a84cb6a8ae" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_AdjustmentsToAdditionalPaidInCapitalWarrantIssued"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SubsidiarySaleOfStockLineItems_9af128fa-eb08-45bf-8e9c-a104fe36d96c" xlink:to="loc_us-gaap_AdjustmentsToAdditionalPaidInCapitalWarrantIssued_328f7984-e132-47fb-b791-90a84cb6a8ae" xlink:type="arc" order="9"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_ClassOfWarrantOrRightExpired_57f361a3-e31a-4a51-9086-17c3684b40f4" xlink:href="espr-20240331.xsd#espr_ClassOfWarrantOrRightExpired"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SubsidiarySaleOfStockLineItems_9af128fa-eb08-45bf-8e9c-a104fe36d96c" xlink:to="loc_espr_ClassOfWarrantOrRightExpired_57f361a3-e31a-4a51-9086-17c3684b40f4" xlink:type="arc" order="10"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ClassOfWarrantOrRightNumberOfSecuritiesCalledByWarrantsOrRights_3acc66f4-4aa6-41d1-888a-abbfef4cb3b7" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ClassOfWarrantOrRightNumberOfSecuritiesCalledByWarrantsOrRights"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SubsidiarySaleOfStockLineItems_9af128fa-eb08-45bf-8e9c-a104fe36d96c" xlink:to="loc_us-gaap_ClassOfWarrantOrRightNumberOfSecuritiesCalledByWarrantsOrRights_3acc66f4-4aa6-41d1-888a-abbfef4cb3b7" xlink:type="arc" order="11"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CommonStockSharesIssued_0be02d3b-e8a9-444f-be14-0066ba5477fd" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_CommonStockSharesIssued"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SubsidiarySaleOfStockLineItems_9af128fa-eb08-45bf-8e9c-a104fe36d96c" xlink:to="loc_us-gaap_CommonStockSharesIssued_0be02d3b-e8a9-444f-be14-0066ba5477fd" xlink:type="arc" order="12"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_CommonStockPurchasableUnderPrefundedWarrants_f583c36b-6cd1-4fbd-9893-878760bf2755" xlink:href="espr-20240331.xsd#espr_CommonStockPurchasableUnderPrefundedWarrants"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SubsidiarySaleOfStockLineItems_9af128fa-eb08-45bf-8e9c-a104fe36d96c" xlink:to="loc_espr_CommonStockPurchasableUnderPrefundedWarrants_f583c36b-6cd1-4fbd-9893-878760bf2755" xlink:type="arc" order="13"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_CommonStockPurchasableUnderWarrants_e6e4b230-2ddd-4257-ab3f-56ecefb8c833" xlink:href="espr-20240331.xsd#espr_CommonStockPurchasableUnderWarrants"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SubsidiarySaleOfStockLineItems_9af128fa-eb08-45bf-8e9c-a104fe36d96c" xlink:to="loc_espr_CommonStockPurchasableUnderWarrants_e6e4b230-2ddd-4257-ab3f-56ecefb8c833" xlink:type="arc" order="14"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_ClassOfWarrantOrRightPurchasePriceOfWarrantsOrRights_f49b07f3-1e68-44d4-9bed-91bbfed635e6" xlink:href="espr-20240331.xsd#espr_ClassOfWarrantOrRightPurchasePriceOfWarrantsOrRights"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SubsidiarySaleOfStockLineItems_9af128fa-eb08-45bf-8e9c-a104fe36d96c" xlink:to="loc_espr_ClassOfWarrantOrRightPurchasePriceOfWarrantsOrRights_f49b07f3-1e68-44d4-9bed-91bbfed635e6" xlink:type="arc" order="15"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CommonStockParOrStatedValuePerShare_d314cfb0-5168-4d83-b96c-552b55bbfa55" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_CommonStockParOrStatedValuePerShare"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SubsidiarySaleOfStockLineItems_9af128fa-eb08-45bf-8e9c-a104fe36d96c" xlink:to="loc_us-gaap_CommonStockParOrStatedValuePerShare_d314cfb0-5168-4d83-b96c-552b55bbfa55" xlink:type="arc" order="16"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_ClassOfWarrantOrRightExercisePriceOfWarrantsOrRightsAdditionalConsideration_b15cf5ed-501a-4cae-bc70-fdd36532e9b9" xlink:href="espr-20240331.xsd#espr_ClassOfWarrantOrRightExercisePriceOfWarrantsOrRightsAdditionalConsideration"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SubsidiarySaleOfStockLineItems_9af128fa-eb08-45bf-8e9c-a104fe36d96c" xlink:to="loc_espr_ClassOfWarrantOrRightExercisePriceOfWarrantsOrRightsAdditionalConsideration_b15cf5ed-501a-4cae-bc70-fdd36532e9b9" xlink:type="arc" order="17"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AdjustmentsToAdditionalPaidInCapitalStockIssuedIssuanceCosts_339cddc1-66b1-47f7-a488-92e484dd74fc" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_AdjustmentsToAdditionalPaidInCapitalStockIssuedIssuanceCosts"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SubsidiarySaleOfStockLineItems_9af128fa-eb08-45bf-8e9c-a104fe36d96c" xlink:to="loc_us-gaap_AdjustmentsToAdditionalPaidInCapitalStockIssuedIssuanceCosts_339cddc1-66b1-47f7-a488-92e484dd74fc" xlink:type="arc" order="18"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ProceedsFromIssuanceOfCommonStock_a58a096b-950b-4960-9ab4-95c2dac09301" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ProceedsFromIssuanceOfCommonStock"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SubsidiarySaleOfStockLineItems_9af128fa-eb08-45bf-8e9c-a104fe36d96c" xlink:to="loc_us-gaap_ProceedsFromIssuanceOfCommonStock_a58a096b-950b-4960-9ab4-95c2dac09301" xlink:type="arc" order="19"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PaymentsForRepurchaseOfPrivatePlacement_4cc4d40e-b439-4ac3-a845-994f6c2c7a7d" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_PaymentsForRepurchaseOfPrivatePlacement"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SubsidiarySaleOfStockLineItems_9af128fa-eb08-45bf-8e9c-a104fe36d96c" xlink:to="loc_us-gaap_PaymentsForRepurchaseOfPrivatePlacement_4cc4d40e-b439-4ac3-a845-994f6c2c7a7d" xlink:type="arc" order="20"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ProceedsFromDebtNetOfIssuanceCosts_28178aad-6c1d-4dec-98f1-30c3525b6abe" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ProceedsFromDebtNetOfIssuanceCosts"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SubsidiarySaleOfStockLineItems_9af128fa-eb08-45bf-8e9c-a104fe36d96c" xlink:to="loc_us-gaap_ProceedsFromDebtNetOfIssuanceCosts_28178aad-6c1d-4dec-98f1-30c3525b6abe" xlink:type="arc" order="21"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_ClassOfWarrantOrRightExercised_8833e302-855e-4ab4-b648-ae18ad8ca8e3" xlink:href="espr-20240331.xsd#espr_ClassOfWarrantOrRightExercised"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SubsidiarySaleOfStockLineItems_9af128fa-eb08-45bf-8e9c-a104fe36d96c" xlink:to="loc_espr_ClassOfWarrantOrRightExercised_8833e302-855e-4ab4-b648-ae18ad8ca8e3" xlink:type="arc" order="22"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.esperion.com/role/StockholdersDeficitSummaryofWarrantsandPrefundedWarrantsOutstandingDetails" xlink:type="simple" xlink:href="espr-20240331.xsd#StockholdersDeficitSummaryofWarrantsandPrefundedWarrantsOutstandingDetails"/>
  <link:definitionLink xlink:role="http://www.esperion.com/role/StockholdersDeficitSummaryofWarrantsandPrefundedWarrantsOutstandingDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SubsidiarySaleOfStockLineItems_adc758ac-1634-4197-bccd-ce0a0b99ee7e" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_SubsidiarySaleOfStockLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SubsidiaryOrEquityMethodInvesteeSaleOfStockBySubsidiaryOrEquityInvesteeTable_e7320bbd-cbe2-4461-bb26-2eeb6ab63dad" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_SubsidiaryOrEquityMethodInvesteeSaleOfStockBySubsidiaryOrEquityInvesteeTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_SubsidiarySaleOfStockLineItems_adc758ac-1634-4197-bccd-ce0a0b99ee7e" xlink:to="loc_us-gaap_SubsidiaryOrEquityMethodInvesteeSaleOfStockBySubsidiaryOrEquityInvesteeTable_e7320bbd-cbe2-4461-bb26-2eeb6ab63dad" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_TypeOfArrangementAxis_9aa9afe3-a485-4419-a89c-1881a198e69f" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_TypeOfArrangementAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_SubsidiaryOrEquityMethodInvesteeSaleOfStockBySubsidiaryOrEquityInvesteeTable_e7320bbd-cbe2-4461-bb26-2eeb6ab63dad" xlink:to="loc_us-gaap_TypeOfArrangementAxis_9aa9afe3-a485-4419-a89c-1881a198e69f" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ArrangementsAndNonarrangementTransactionsMember_9aa9afe3-a485-4419-a89c-1881a198e69f_default" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ArrangementsAndNonarrangementTransactionsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_TypeOfArrangementAxis_9aa9afe3-a485-4419-a89c-1881a198e69f" xlink:to="loc_us-gaap_ArrangementsAndNonarrangementTransactionsMember_9aa9afe3-a485-4419-a89c-1881a198e69f_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ArrangementsAndNonarrangementTransactionsMember_bdf44038-deba-4533-8c52-3cffb3d62b66" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ArrangementsAndNonarrangementTransactionsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_TypeOfArrangementAxis_9aa9afe3-a485-4419-a89c-1881a198e69f" xlink:to="loc_us-gaap_ArrangementsAndNonarrangementTransactionsMember_bdf44038-deba-4533-8c52-3cffb3d62b66" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_WarrantAmendmentAgreementsMember_32d3c028-ee27-4402-be0b-432b3bde217a" xlink:href="espr-20240331.xsd#espr_WarrantAmendmentAgreementsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ArrangementsAndNonarrangementTransactionsMember_bdf44038-deba-4533-8c52-3cffb3d62b66" xlink:to="loc_espr_WarrantAmendmentAgreementsMember_32d3c028-ee27-4402-be0b-432b3bde217a" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_SecuritiesPurchaseAgreementMember_97120a0c-1188-407e-9036-fe5a9e41ce19" xlink:href="espr-20240331.xsd#espr_SecuritiesPurchaseAgreementMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ArrangementsAndNonarrangementTransactionsMember_bdf44038-deba-4533-8c52-3cffb3d62b66" xlink:to="loc_espr_SecuritiesPurchaseAgreementMember_97120a0c-1188-407e-9036-fe5a9e41ce19" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ClassOfWarrantOrRightOutstanding_8d663a45-7a71-481a-a08e-ec8565f1751c" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ClassOfWarrantOrRightOutstanding"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SubsidiarySaleOfStockLineItems_adc758ac-1634-4197-bccd-ce0a0b99ee7e" xlink:to="loc_us-gaap_ClassOfWarrantOrRightOutstanding_8d663a45-7a71-481a-a08e-ec8565f1751c" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ClassOfWarrantOrRightExercisePriceOfWarrantsOrRights1_822b6193-1897-4350-aece-c4fbc5a8abf0" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ClassOfWarrantOrRightExercisePriceOfWarrantsOrRights1"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SubsidiarySaleOfStockLineItems_adc758ac-1634-4197-bccd-ce0a0b99ee7e" xlink:to="loc_us-gaap_ClassOfWarrantOrRightExercisePriceOfWarrantsOrRights1_822b6193-1897-4350-aece-c4fbc5a8abf0" xlink:type="arc" order="1"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.esperion.com/role/NetIncomeLossPerCommonShareCalculationofBasicandDilutedLossIncomePerShareDetails" xlink:type="simple" xlink:href="espr-20240331.xsd#NetIncomeLossPerCommonShareCalculationofBasicandDilutedLossIncomePerShareDetails"/>
  <link:definitionLink xlink:role="http://www.esperion.com/role/NetIncomeLossPerCommonShareCalculationofBasicandDilutedLossIncomePerShareDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EarningsPerShareBasicLineItems_55b0b356-02ec-4d8d-b7d0-5c5ce67e9625" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_EarningsPerShareBasicLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfEarningsPerShareBasicByCommonClassTable_f228dafc-d726-4ad2-ab94-0edeead5c2a9" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ScheduleOfEarningsPerShareBasicByCommonClassTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_EarningsPerShareBasicLineItems_55b0b356-02ec-4d8d-b7d0-5c5ce67e9625" xlink:to="loc_us-gaap_ScheduleOfEarningsPerShareBasicByCommonClassTable_f228dafc-d726-4ad2-ab94-0edeead5c2a9" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AwardTypeAxis_2dff2db6-1dd6-4972-af38-434bc652d634" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_AwardTypeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfEarningsPerShareBasicByCommonClassTable_f228dafc-d726-4ad2-ab94-0edeead5c2a9" xlink:to="loc_us-gaap_AwardTypeAxis_2dff2db6-1dd6-4972-af38-434bc652d634" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_2dff2db6-1dd6-4972-af38-434bc652d634_default" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_AwardTypeAxis_2dff2db6-1dd6-4972-af38-434bc652d634" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_2dff2db6-1dd6-4972-af38-434bc652d634_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_774cc9dc-d4a6-4219-97b6-12f0dd4d97b6" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_AwardTypeAxis_2dff2db6-1dd6-4972-af38-434bc652d634" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_774cc9dc-d4a6-4219-97b6-12f0dd4d97b6" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EmployeeStockOptionMember_f6fe79e9-b2f8-465e-826e-bf5d9e967f00" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_EmployeeStockOptionMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_774cc9dc-d4a6-4219-97b6-12f0dd4d97b6" xlink:to="loc_us-gaap_EmployeeStockOptionMember_f6fe79e9-b2f8-465e-826e-bf5d9e967f00" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_ShareBasedPaymentArrangementOptionPerformanceBasedMember_3fa32316-a7de-4beb-a58f-b70999056838" xlink:href="espr-20240331.xsd#espr_ShareBasedPaymentArrangementOptionPerformanceBasedMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_774cc9dc-d4a6-4219-97b6-12f0dd4d97b6" xlink:to="loc_espr_ShareBasedPaymentArrangementOptionPerformanceBasedMember_3fa32316-a7de-4beb-a58f-b70999056838" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_UnvestedRestrictedStockAndRestrictedStockUnitsMember_d8e2c7a5-b094-432f-a0e8-da16ab871c93" xlink:href="espr-20240331.xsd#espr_UnvestedRestrictedStockAndRestrictedStockUnitsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_774cc9dc-d4a6-4219-97b6-12f0dd4d97b6" xlink:to="loc_espr_UnvestedRestrictedStockAndRestrictedStockUnitsMember_d8e2c7a5-b094-432f-a0e8-da16ab871c93" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PerformanceSharesMember_bd0f2dba-8a1b-47ab-b373-261f32fd5d42" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_PerformanceSharesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_774cc9dc-d4a6-4219-97b6-12f0dd4d97b6" xlink:to="loc_us-gaap_PerformanceSharesMember_bd0f2dba-8a1b-47ab-b373-261f32fd5d42" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_NetIncomeLossAvailableToCommonStockholdersBasic_8efbc5a6-8ea6-429c-ae97-0972ec6571f4" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_NetIncomeLossAvailableToCommonStockholdersBasic"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_EarningsPerShareBasicLineItems_55b0b356-02ec-4d8d-b7d0-5c5ce67e9625" xlink:to="loc_us-gaap_NetIncomeLossAvailableToCommonStockholdersBasic_8efbc5a6-8ea6-429c-ae97-0972ec6571f4" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_NetIncomeLossAttributableToParentDilutedAbstract_6ea7f43f-ba21-4d98-ae46-ba7e21f77baa" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_NetIncomeLossAttributableToParentDilutedAbstract"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_EarningsPerShareBasicLineItems_55b0b356-02ec-4d8d-b7d0-5c5ce67e9625" xlink:to="loc_us-gaap_NetIncomeLossAttributableToParentDilutedAbstract_6ea7f43f-ba21-4d98-ae46-ba7e21f77baa" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_InterestOnConvertibleDebtNetOfTax_1f0502df-dff7-4626-81e7-049bcc99ced5" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_InterestOnConvertibleDebtNetOfTax"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_NetIncomeLossAttributableToParentDilutedAbstract_6ea7f43f-ba21-4d98-ae46-ba7e21f77baa" xlink:to="loc_us-gaap_InterestOnConvertibleDebtNetOfTax_1f0502df-dff7-4626-81e7-049bcc99ced5" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_NetIncomeLossAvailableToCommonStockholdersDiluted_2b152c46-b448-444e-8c02-d5295b2d0d1c" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_NetIncomeLossAvailableToCommonStockholdersDiluted"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_EarningsPerShareBasicLineItems_55b0b356-02ec-4d8d-b7d0-5c5ce67e9625" xlink:to="loc_us-gaap_NetIncomeLossAvailableToCommonStockholdersDiluted_2b152c46-b448-444e-8c02-d5295b2d0d1c" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_WeightedAverageNumberOfSharesOutstandingBasic_8bae725d-9298-46b4-baed-68fb40d829c0" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_WeightedAverageNumberOfSharesOutstandingBasic"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_EarningsPerShareBasicLineItems_55b0b356-02ec-4d8d-b7d0-5c5ce67e9625" xlink:to="loc_us-gaap_WeightedAverageNumberOfSharesOutstandingBasic_8bae725d-9298-46b4-baed-68fb40d829c0" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_WeightedAverageNumberDilutedSharesOutstandingAdjustmentAbstract_0f5e2035-e292-463f-900e-b4c5f337a1f1" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_WeightedAverageNumberDilutedSharesOutstandingAdjustmentAbstract"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_EarningsPerShareBasicLineItems_55b0b356-02ec-4d8d-b7d0-5c5ce67e9625" xlink:to="loc_us-gaap_WeightedAverageNumberDilutedSharesOutstandingAdjustmentAbstract_0f5e2035-e292-463f-900e-b4c5f337a1f1" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncrementalCommonSharesAttributableToCallOptionsAndWarrants_26636145-d188-41ea-ae10-1f0247b91dea" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_IncrementalCommonSharesAttributableToCallOptionsAndWarrants"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_WeightedAverageNumberDilutedSharesOutstandingAdjustmentAbstract_0f5e2035-e292-463f-900e-b4c5f337a1f1" xlink:to="loc_us-gaap_IncrementalCommonSharesAttributableToCallOptionsAndWarrants_26636145-d188-41ea-ae10-1f0247b91dea" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncrementalCommonSharesAttributableToConversionOfDebtSecurities_737d655a-51ab-4a61-9ba0-6fb34b8e611e" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_IncrementalCommonSharesAttributableToConversionOfDebtSecurities"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_WeightedAverageNumberDilutedSharesOutstandingAdjustmentAbstract_0f5e2035-e292-463f-900e-b4c5f337a1f1" xlink:to="loc_us-gaap_IncrementalCommonSharesAttributableToConversionOfDebtSecurities_737d655a-51ab-4a61-9ba0-6fb34b8e611e" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncrementalCommonSharesAttributableToShareBasedPaymentArrangements_99ab6469-acef-4a9c-9a78-9c1bf40f9521" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_IncrementalCommonSharesAttributableToShareBasedPaymentArrangements"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_WeightedAverageNumberDilutedSharesOutstandingAdjustmentAbstract_0f5e2035-e292-463f-900e-b4c5f337a1f1" xlink:to="loc_us-gaap_IncrementalCommonSharesAttributableToShareBasedPaymentArrangements_99ab6469-acef-4a9c-9a78-9c1bf40f9521" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_WeightedAverageNumberDilutedSharesOutstandingAdjustment_747903ea-78f6-4a59-bf4a-a585c758a7ae" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_WeightedAverageNumberDilutedSharesOutstandingAdjustment"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_EarningsPerShareBasicLineItems_55b0b356-02ec-4d8d-b7d0-5c5ce67e9625" xlink:to="loc_us-gaap_WeightedAverageNumberDilutedSharesOutstandingAdjustment_747903ea-78f6-4a59-bf4a-a585c758a7ae" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_WeightedAverageNumberOfDilutedSharesOutstanding_93b3018f-7d20-41e5-a827-21fc80231300" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_WeightedAverageNumberOfDilutedSharesOutstanding"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_EarningsPerShareBasicLineItems_55b0b356-02ec-4d8d-b7d0-5c5ce67e9625" xlink:to="loc_us-gaap_WeightedAverageNumberOfDilutedSharesOutstanding_93b3018f-7d20-41e5-a827-21fc80231300" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EarningsPerShareBasic_c4c6051b-7baf-415c-b31d-1202240029e5" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_EarningsPerShareBasic"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_EarningsPerShareBasicLineItems_55b0b356-02ec-4d8d-b7d0-5c5ce67e9625" xlink:to="loc_us-gaap_EarningsPerShareBasic_c4c6051b-7baf-415c-b31d-1202240029e5" xlink:type="arc" order="7"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EarningsPerShareDiluted_96b53eea-713d-442a-b1f7-8250028b3f9a" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_EarningsPerShareDiluted"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_EarningsPerShareBasicLineItems_55b0b356-02ec-4d8d-b7d0-5c5ce67e9625" xlink:to="loc_us-gaap_EarningsPerShareDiluted_96b53eea-713d-442a-b1f7-8250028b3f9a" xlink:type="arc" order="8"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.esperion.com/role/NetIncomeLossPerCommonShareDetails" xlink:type="simple" xlink:href="espr-20240331.xsd#NetIncomeLossPerCommonShareDetails"/>
  <link:definitionLink xlink:role="http://www.esperion.com/role/NetIncomeLossPerCommonShareDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareLineItems_6ba5c97b-d7b8-42df-bd0e-5339af1b8a5e" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfAntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareTable_bbe125bb-ee7b-472a-a282-9860b04cc555" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ScheduleOfAntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareLineItems_6ba5c97b-d7b8-42df-bd0e-5339af1b8a5e" xlink:to="loc_us-gaap_ScheduleOfAntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareTable_bbe125bb-ee7b-472a-a282-9860b04cc555" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareByAntidilutiveSecuritiesAxis_99f5a504-3adf-45e9-beb8-8dca6ac0557d" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareByAntidilutiveSecuritiesAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfAntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareTable_bbe125bb-ee7b-472a-a282-9860b04cc555" xlink:to="loc_us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareByAntidilutiveSecuritiesAxis_99f5a504-3adf-45e9-beb8-8dca6ac0557d" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AntidilutiveSecuritiesNameDomain_99f5a504-3adf-45e9-beb8-8dca6ac0557d_default" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_AntidilutiveSecuritiesNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareByAntidilutiveSecuritiesAxis_99f5a504-3adf-45e9-beb8-8dca6ac0557d" xlink:to="loc_us-gaap_AntidilutiveSecuritiesNameDomain_99f5a504-3adf-45e9-beb8-8dca6ac0557d_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AntidilutiveSecuritiesNameDomain_35b07824-5807-4e37-b989-6b9b6127ec31" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_AntidilutiveSecuritiesNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareByAntidilutiveSecuritiesAxis_99f5a504-3adf-45e9-beb8-8dca6ac0557d" xlink:to="loc_us-gaap_AntidilutiveSecuritiesNameDomain_35b07824-5807-4e37-b989-6b9b6127ec31" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EmployeeStockOptionMember_116b22b7-2298-4a16-9ebe-37a8a1239e88" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_EmployeeStockOptionMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AntidilutiveSecuritiesNameDomain_35b07824-5807-4e37-b989-6b9b6127ec31" xlink:to="loc_us-gaap_EmployeeStockOptionMember_116b22b7-2298-4a16-9ebe-37a8a1239e88" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_ShareBasedPaymentArrangementOptionPerformanceBasedMember_0075c698-38e8-4a1c-89ea-97c46cbdd088" xlink:href="espr-20240331.xsd#espr_ShareBasedPaymentArrangementOptionPerformanceBasedMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AntidilutiveSecuritiesNameDomain_35b07824-5807-4e37-b989-6b9b6127ec31" xlink:to="loc_espr_ShareBasedPaymentArrangementOptionPerformanceBasedMember_0075c698-38e8-4a1c-89ea-97c46cbdd088" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_UnvestedRestrictedStockAndRestrictedStockUnitsMember_4d0acb10-6b94-478d-b844-92b566522e04" xlink:href="espr-20240331.xsd#espr_UnvestedRestrictedStockAndRestrictedStockUnitsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AntidilutiveSecuritiesNameDomain_35b07824-5807-4e37-b989-6b9b6127ec31" xlink:to="loc_espr_UnvestedRestrictedStockAndRestrictedStockUnitsMember_4d0acb10-6b94-478d-b844-92b566522e04" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PerformanceSharesMember_bd416be5-4656-458e-bd71-3de5a7f096c7" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_PerformanceSharesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AntidilutiveSecuritiesNameDomain_35b07824-5807-4e37-b989-6b9b6127ec31" xlink:to="loc_us-gaap_PerformanceSharesMember_bd416be5-4656-458e-bd71-3de5a7f096c7" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EmployeeStockMember_38719b5c-3ac2-4679-b5ef-da2f108fdf4d" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_EmployeeStockMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AntidilutiveSecuritiesNameDomain_35b07824-5807-4e37-b989-6b9b6127ec31" xlink:to="loc_us-gaap_EmployeeStockMember_38719b5c-3ac2-4679-b5ef-da2f108fdf4d" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ConvertibleDebtSecuritiesMember_0ad847d7-5100-4b87-bd5d-8bcb843728a7" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ConvertibleDebtSecuritiesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AntidilutiveSecuritiesNameDomain_35b07824-5807-4e37-b989-6b9b6127ec31" xlink:to="loc_us-gaap_ConvertibleDebtSecuritiesMember_0ad847d7-5100-4b87-bd5d-8bcb843728a7" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_WarrantMember_4f519804-b4d7-4ef2-9082-ee2215bcbf74" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_WarrantMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AntidilutiveSecuritiesNameDomain_35b07824-5807-4e37-b989-6b9b6127ec31" xlink:to="loc_us-gaap_WarrantMember_4f519804-b4d7-4ef2-9082-ee2215bcbf74" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AwardTypeAxis_8ba59fb5-59ae-4a6a-afbc-cfd5428acf19" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_AwardTypeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfAntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareTable_bbe125bb-ee7b-472a-a282-9860b04cc555" xlink:to="loc_us-gaap_AwardTypeAxis_8ba59fb5-59ae-4a6a-afbc-cfd5428acf19" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_8ba59fb5-59ae-4a6a-afbc-cfd5428acf19_default" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_AwardTypeAxis_8ba59fb5-59ae-4a6a-afbc-cfd5428acf19" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_8ba59fb5-59ae-4a6a-afbc-cfd5428acf19_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_db5c5d8e-b06a-4f61-b56d-f564f62102fc" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_AwardTypeAxis_8ba59fb5-59ae-4a6a-afbc-cfd5428acf19" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_db5c5d8e-b06a-4f61-b56d-f564f62102fc" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EmployeeStockOptionMember_d66304c5-cf66-43c1-bc37-c9edbbbe3efe" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_EmployeeStockOptionMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_db5c5d8e-b06a-4f61-b56d-f564f62102fc" xlink:to="loc_us-gaap_EmployeeStockOptionMember_d66304c5-cf66-43c1-bc37-c9edbbbe3efe" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareAmount_78d3fda2-8d83-4033-b5fa-cdbc873047df" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareAmount"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareLineItems_6ba5c97b-d7b8-42df-bd0e-5339af1b8a5e" xlink:to="loc_us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareAmount_78d3fda2-8d83-4033-b5fa-cdbc873047df" xlink:type="arc" order="0"/>
  </link:definitionLink>
</link:linkbase>
