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

<!--XBRL Document Created with the Workiva Platform-->
<!--Copyright 2025 Workiva-->
<!--r:85076e73-f8a7-4eef-b204-b2d55fd3ac89,g:6efb0e90-3c9f-4e43-b925-c531f2aa0a86-->
<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/CondensedStatementsofOperationsandComprehensiveLoss" xlink:type="simple" xlink:href="espr-20250630.xsd#CondensedStatementsofOperationsandComprehensiveLoss"/>
  <link:definitionLink xlink:role="http://www.esperion.com/role/CondensedStatementsofOperationsandComprehensiveLoss" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StatementLineItems_8de38f0e-f1e6-417d-b3fa-91d147d42429" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_StatementLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StatementTable_b7ca29a0-2ccd-4c5e-983b-c379b032b3fc" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_StatementTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_StatementLineItems_8de38f0e-f1e6-417d-b3fa-91d147d42429" xlink:to="loc_us-gaap_StatementTable_b7ca29a0-2ccd-4c5e-983b-c379b032b3fc" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductOrServiceAxis_1f656a57-67f5-4c97-81bf-a3aa6ef92781" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_ProductOrServiceAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_StatementTable_b7ca29a0-2ccd-4c5e-983b-c379b032b3fc" xlink:to="loc_srt_ProductOrServiceAxis_1f656a57-67f5-4c97-81bf-a3aa6ef92781" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductsAndServicesDomain_1f656a57-67f5-4c97-81bf-a3aa6ef92781_default" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_ProductsAndServicesDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_ProductOrServiceAxis_1f656a57-67f5-4c97-81bf-a3aa6ef92781" xlink:to="loc_srt_ProductsAndServicesDomain_1f656a57-67f5-4c97-81bf-a3aa6ef92781_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductsAndServicesDomain_7b69e7cf-bb17-4ae5-912c-fa92c6b26a62" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_ProductsAndServicesDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_ProductOrServiceAxis_1f656a57-67f5-4c97-81bf-a3aa6ef92781" xlink:to="loc_srt_ProductsAndServicesDomain_7b69e7cf-bb17-4ae5-912c-fa92c6b26a62" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ProductMember_e3ae86a9-3e36-49ed-8ca2-e23dd910f079" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ProductMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ProductsAndServicesDomain_7b69e7cf-bb17-4ae5-912c-fa92c6b26a62" xlink:to="loc_us-gaap_ProductMember_e3ae86a9-3e36-49ed-8ca2-e23dd910f079" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_CollaborationRevenueMember_48524b86-a03a-49e6-97a7-9346b3509860" xlink:href="espr-20250630.xsd#espr_CollaborationRevenueMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ProductsAndServicesDomain_7b69e7cf-bb17-4ae5-912c-fa92c6b26a62" xlink:to="loc_espr_CollaborationRevenueMember_48524b86-a03a-49e6-97a7-9346b3509860" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RevenuesAbstract_73018345-bb07-4111-a401-635c0af9268f" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_RevenuesAbstract"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_8de38f0e-f1e6-417d-b3fa-91d147d42429" xlink:to="loc_us-gaap_RevenuesAbstract_73018345-bb07-4111-a401-635c0af9268f" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax_98156c03-1222-4275-8e2c-d7680484b819" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_RevenuesAbstract_73018345-bb07-4111-a401-635c0af9268f" xlink:to="loc_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax_98156c03-1222-4275-8e2c-d7680484b819" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OperatingExpensesAbstract_f6278f11-37a0-4838-958d-5167ee837bde" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_OperatingExpensesAbstract"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_8de38f0e-f1e6-417d-b3fa-91d147d42429" xlink:to="loc_us-gaap_OperatingExpensesAbstract_f6278f11-37a0-4838-958d-5167ee837bde" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OtherCostAndExpenseOperating_d604a864-f27c-48e6-acd6-3b3e77eb035a" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_OtherCostAndExpenseOperating"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_OperatingExpensesAbstract_f6278f11-37a0-4838-958d-5167ee837bde" xlink:to="loc_us-gaap_OtherCostAndExpenseOperating_d604a864-f27c-48e6-acd6-3b3e77eb035a" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ResearchAndDevelopmentExpenseExcludingAcquiredInProcessCost_4202f192-5c07-4752-89cd-857eed6a6ba1" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ResearchAndDevelopmentExpenseExcludingAcquiredInProcessCost"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_OperatingExpensesAbstract_f6278f11-37a0-4838-958d-5167ee837bde" xlink:to="loc_us-gaap_ResearchAndDevelopmentExpenseExcludingAcquiredInProcessCost_4202f192-5c07-4752-89cd-857eed6a6ba1" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SellingGeneralAndAdministrativeExpense_f59a4cd4-2bce-4f94-8c2b-b87f5e893580" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_SellingGeneralAndAdministrativeExpense"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_OperatingExpensesAbstract_f6278f11-37a0-4838-958d-5167ee837bde" xlink:to="loc_us-gaap_SellingGeneralAndAdministrativeExpense_f59a4cd4-2bce-4f94-8c2b-b87f5e893580" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OperatingExpenses_5bf3f418-7c39-4493-84d6-0707e81ceb7c" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_OperatingExpenses"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_OperatingExpensesAbstract_f6278f11-37a0-4838-958d-5167ee837bde" xlink:to="loc_us-gaap_OperatingExpenses_5bf3f418-7c39-4493-84d6-0707e81ceb7c" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OperatingIncomeLoss_29bb2ef5-aece-460a-9810-7d0632c4fc2e" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_OperatingIncomeLoss"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_8de38f0e-f1e6-417d-b3fa-91d147d42429" xlink:to="loc_us-gaap_OperatingIncomeLoss_29bb2ef5-aece-460a-9810-7d0632c4fc2e" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_InterestExpenseNonoperating_2d88d08a-955d-4ff2-a2b2-6ee2bf6bb9d1" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_InterestExpenseNonoperating"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_8de38f0e-f1e6-417d-b3fa-91d147d42429" xlink:to="loc_us-gaap_InterestExpenseNonoperating_2d88d08a-955d-4ff2-a2b2-6ee2bf6bb9d1" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_GainsLossesOnExtinguishmentOfDebt_b46c0240-7ed2-4be7-b2f1-677eb331baf9" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_GainsLossesOnExtinguishmentOfDebt"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_8de38f0e-f1e6-417d-b3fa-91d147d42429" xlink:to="loc_us-gaap_GainsLossesOnExtinguishmentOfDebt_b46c0240-7ed2-4be7-b2f1-677eb331baf9" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OtherNonoperatingIncomeExpense_863cf6c4-151a-4066-8bcc-2f5b5f6ddfcc" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_OtherNonoperatingIncomeExpense"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_8de38f0e-f1e6-417d-b3fa-91d147d42429" xlink:to="loc_us-gaap_OtherNonoperatingIncomeExpense_863cf6c4-151a-4066-8bcc-2f5b5f6ddfcc" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_NetIncomeLoss_91c5bbc5-dea2-49bc-a784-e6cc39c9313a" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_NetIncomeLoss"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_8de38f0e-f1e6-417d-b3fa-91d147d42429" xlink:to="loc_us-gaap_NetIncomeLoss_91c5bbc5-dea2-49bc-a784-e6cc39c9313a" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EarningsPerShareBasic_357e9b6c-644b-49e6-ae97-d8bf23692b0b" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_EarningsPerShareBasic"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_8de38f0e-f1e6-417d-b3fa-91d147d42429" xlink:to="loc_us-gaap_EarningsPerShareBasic_357e9b6c-644b-49e6-ae97-d8bf23692b0b" xlink:type="arc" order="7"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EarningsPerShareDiluted_6b4f9db8-e6c2-4033-84b9-47e3a7ef9876" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_EarningsPerShareDiluted"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_8de38f0e-f1e6-417d-b3fa-91d147d42429" xlink:to="loc_us-gaap_EarningsPerShareDiluted_6b4f9db8-e6c2-4033-84b9-47e3a7ef9876" xlink:type="arc" order="8"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_WeightedAverageNumberOfSharesOutstandingBasic_d970c204-c68f-4c3b-b420-a6fe2aef7eab" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_WeightedAverageNumberOfSharesOutstandingBasic"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_8de38f0e-f1e6-417d-b3fa-91d147d42429" xlink:to="loc_us-gaap_WeightedAverageNumberOfSharesOutstandingBasic_d970c204-c68f-4c3b-b420-a6fe2aef7eab" xlink:type="arc" order="9"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_WeightedAverageNumberOfDilutedSharesOutstanding_f81c7ce2-5350-4205-8a4f-d3bc40000f11" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_WeightedAverageNumberOfDilutedSharesOutstanding"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_8de38f0e-f1e6-417d-b3fa-91d147d42429" xlink:to="loc_us-gaap_WeightedAverageNumberOfDilutedSharesOutstanding_f81c7ce2-5350-4205-8a4f-d3bc40000f11" xlink:type="arc" order="10"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ComprehensiveIncomeNetOfTax_f0a4d7e4-8e87-4c15-991a-514f80ba806e" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ComprehensiveIncomeNetOfTax"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_8de38f0e-f1e6-417d-b3fa-91d147d42429" xlink:to="loc_us-gaap_ComprehensiveIncomeNetOfTax_f0a4d7e4-8e87-4c15-991a-514f80ba806e" xlink:type="arc" order="11"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.esperion.com/role/CondensedStatementsofStockholdersDeficit" xlink:type="simple" xlink:href="espr-20250630.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_ce7a2b35-8672-4428-ab76-2094e3e25e92" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_StatementLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StatementTable_196e3f0c-4d1b-4691-a54d-93dfbc4353a0" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_StatementTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_StatementLineItems_ce7a2b35-8672-4428-ab76-2094e3e25e92" xlink:to="loc_us-gaap_StatementTable_196e3f0c-4d1b-4691-a54d-93dfbc4353a0" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StatementEquityComponentsAxis_b1cefd9a-0e46-41a9-92de-074bb4a8e2bc" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_StatementEquityComponentsAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_StatementTable_196e3f0c-4d1b-4691-a54d-93dfbc4353a0" xlink:to="loc_us-gaap_StatementEquityComponentsAxis_b1cefd9a-0e46-41a9-92de-074bb4a8e2bc" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EquityComponentDomain_b1cefd9a-0e46-41a9-92de-074bb4a8e2bc_default" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_EquityComponentDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_StatementEquityComponentsAxis_b1cefd9a-0e46-41a9-92de-074bb4a8e2bc" xlink:to="loc_us-gaap_EquityComponentDomain_b1cefd9a-0e46-41a9-92de-074bb4a8e2bc_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EquityComponentDomain_cc9d7259-bbfc-4936-9a58-2c86fdb0a9b8" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_EquityComponentDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_StatementEquityComponentsAxis_b1cefd9a-0e46-41a9-92de-074bb4a8e2bc" xlink:to="loc_us-gaap_EquityComponentDomain_cc9d7259-bbfc-4936-9a58-2c86fdb0a9b8" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CommonStockMember_9620186c-91e7-4d96-874e-5de6ed0c6576" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_CommonStockMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_EquityComponentDomain_cc9d7259-bbfc-4936-9a58-2c86fdb0a9b8" xlink:to="loc_us-gaap_CommonStockMember_9620186c-91e7-4d96-874e-5de6ed0c6576" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AdditionalPaidInCapitalMember_47f83994-8e51-4528-b54d-c6e4dfee34d4" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_AdditionalPaidInCapitalMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_EquityComponentDomain_cc9d7259-bbfc-4936-9a58-2c86fdb0a9b8" xlink:to="loc_us-gaap_AdditionalPaidInCapitalMember_47f83994-8e51-4528-b54d-c6e4dfee34d4" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RetainedEarningsMember_6efebeab-2236-4eb7-b66d-6f9a1956220a" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_RetainedEarningsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_EquityComponentDomain_cc9d7259-bbfc-4936-9a58-2c86fdb0a9b8" xlink:to="loc_us-gaap_RetainedEarningsMember_6efebeab-2236-4eb7-b66d-6f9a1956220a" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AccumulatedOtherComprehensiveIncomeMember_3701ac85-6caf-43d6-9318-0f01fd46f2d0" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_AccumulatedOtherComprehensiveIncomeMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_EquityComponentDomain_cc9d7259-bbfc-4936-9a58-2c86fdb0a9b8" xlink:to="loc_us-gaap_AccumulatedOtherComprehensiveIncomeMember_3701ac85-6caf-43d6-9318-0f01fd46f2d0" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_TreasuryStockCommonMember_30a106e7-7e30-4d64-b56a-70e47d1a5888" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_TreasuryStockCommonMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_EquityComponentDomain_cc9d7259-bbfc-4936-9a58-2c86fdb0a9b8" xlink:to="loc_us-gaap_TreasuryStockCommonMember_30a106e7-7e30-4d64-b56a-70e47d1a5888" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_51a8d646-2032-4cb6-a8fa-ebe05a2cd0a5" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_IncreaseDecreaseInStockholdersEquityRollForward"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_ce7a2b35-8672-4428-ab76-2094e3e25e92" xlink:to="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_51a8d646-2032-4cb6-a8fa-ebe05a2cd0a5" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SharesOutstanding_25038399-476c-45a9-94ca-1dcfbd7c3da6" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_SharesOutstanding"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_51a8d646-2032-4cb6-a8fa-ebe05a2cd0a5" xlink:to="loc_us-gaap_SharesOutstanding_25038399-476c-45a9-94ca-1dcfbd7c3da6" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StockholdersEquity_f82f89ec-da07-466c-938a-5cffd1f8cac8" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_StockholdersEquity"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_51a8d646-2032-4cb6-a8fa-ebe05a2cd0a5" xlink:to="loc_us-gaap_StockholdersEquity_f82f89ec-da07-466c-938a-5cffd1f8cac8" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StockIssuedDuringPeriodSharesRestrictedStockAwardGross_0e52a742-370d-4f7c-8bd5-da867d096f96" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_StockIssuedDuringPeriodSharesRestrictedStockAwardGross"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_51a8d646-2032-4cb6-a8fa-ebe05a2cd0a5" xlink:to="loc_us-gaap_StockIssuedDuringPeriodSharesRestrictedStockAwardGross_0e52a742-370d-4f7c-8bd5-da867d096f96" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StockIssuedDuringPeriodValueRestrictedStockAwardGross_77b0bdbf-48bc-47d7-b5b8-13ae196c0fcd" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_StockIssuedDuringPeriodValueRestrictedStockAwardGross"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_51a8d646-2032-4cb6-a8fa-ebe05a2cd0a5" xlink:to="loc_us-gaap_StockIssuedDuringPeriodValueRestrictedStockAwardGross_77b0bdbf-48bc-47d7-b5b8-13ae196c0fcd" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StockIssuedDuringPeriodSharesEmployeeStockPurchasePlans_9d20734e-ef12-4534-b861-86f6af7c42d6" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_StockIssuedDuringPeriodSharesEmployeeStockPurchasePlans"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_51a8d646-2032-4cb6-a8fa-ebe05a2cd0a5" xlink:to="loc_us-gaap_StockIssuedDuringPeriodSharesEmployeeStockPurchasePlans_9d20734e-ef12-4534-b861-86f6af7c42d6" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StockIssuedDuringPeriodValueEmployeeStockPurchasePlan_b0166e0d-527f-4058-b737-cc4452229e87" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_StockIssuedDuringPeriodValueEmployeeStockPurchasePlan"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_51a8d646-2032-4cb6-a8fa-ebe05a2cd0a5" xlink:to="loc_us-gaap_StockIssuedDuringPeriodValueEmployeeStockPurchasePlan_b0166e0d-527f-4058-b737-cc4452229e87" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue_26afb3a4-49f7-4953-abe1-7b3d99c2afed" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_51a8d646-2032-4cb6-a8fa-ebe05a2cd0a5" xlink:to="loc_us-gaap_AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue_26afb3a4-49f7-4953-abe1-7b3d99c2afed" xlink:type="arc" order="7"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StockIssuedDuringPeriodSharesNewIssues_e27de572-c788-4247-90c1-8aa6dd96e0d9" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_StockIssuedDuringPeriodSharesNewIssues"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_51a8d646-2032-4cb6-a8fa-ebe05a2cd0a5" xlink:to="loc_us-gaap_StockIssuedDuringPeriodSharesNewIssues_e27de572-c788-4247-90c1-8aa6dd96e0d9" xlink:type="arc" order="8"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StockIssuedDuringPeriodValueNewIssues_0f083007-df6b-4984-8dd5-1ace556e0036" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_StockIssuedDuringPeriodValueNewIssues"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_51a8d646-2032-4cb6-a8fa-ebe05a2cd0a5" xlink:to="loc_us-gaap_StockIssuedDuringPeriodValueNewIssues_0f083007-df6b-4984-8dd5-1ace556e0036" xlink:type="arc" order="9"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StockIssuedDuringPeriodSharesStockOptionsExercised_9926061f-cf92-498f-934e-7a4893b2629e" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_StockIssuedDuringPeriodSharesStockOptionsExercised"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_51a8d646-2032-4cb6-a8fa-ebe05a2cd0a5" xlink:to="loc_us-gaap_StockIssuedDuringPeriodSharesStockOptionsExercised_9926061f-cf92-498f-934e-7a4893b2629e" xlink:type="arc" order="10"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StockIssuedDuringPeriodValueStockOptionsExercised_5a00f8f8-c5b3-4d5c-874a-a2fd038f237e" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_StockIssuedDuringPeriodValueStockOptionsExercised"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_51a8d646-2032-4cb6-a8fa-ebe05a2cd0a5" xlink:to="loc_us-gaap_StockIssuedDuringPeriodValueStockOptionsExercised_5a00f8f8-c5b3-4d5c-874a-a2fd038f237e" xlink:type="arc" order="11"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_StockIssuedDuringPeriodSharesWarrantExercises_0b62a8af-a246-4098-bb8d-bf8dba3fe3e6" xlink:href="espr-20250630.xsd#espr_StockIssuedDuringPeriodSharesWarrantExercises"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_51a8d646-2032-4cb6-a8fa-ebe05a2cd0a5" xlink:to="loc_espr_StockIssuedDuringPeriodSharesWarrantExercises_0b62a8af-a246-4098-bb8d-bf8dba3fe3e6" xlink:type="arc" order="12"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_StockIssuedDuringPeriodValueWarrantExercises_a6c148a7-62fa-40d3-8f60-3d3a507a43e6" xlink:href="espr-20250630.xsd#espr_StockIssuedDuringPeriodValueWarrantExercises"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_51a8d646-2032-4cb6-a8fa-ebe05a2cd0a5" xlink:to="loc_espr_StockIssuedDuringPeriodValueWarrantExercises_a6c148a7-62fa-40d3-8f60-3d3a507a43e6" xlink:type="arc" order="13"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_NetIncomeLoss_3a4a5b5e-c8eb-49bd-81f1-983d6425559a" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_NetIncomeLoss"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_51a8d646-2032-4cb6-a8fa-ebe05a2cd0a5" xlink:to="loc_us-gaap_NetIncomeLoss_3a4a5b5e-c8eb-49bd-81f1-983d6425559a" xlink:type="arc" order="14"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SharesOutstanding_5e51621b-77a3-4226-8eda-195e8856c6cc" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_SharesOutstanding"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StockholdersEquity_6b710344-352e-4ebf-8e8d-aa48924baa4d" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_StockholdersEquity"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.esperion.com/role/SummaryofSignificantAccountingPoliciesDetails" xlink:type="simple" xlink:href="espr-20250630.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_e07f29ff-4dc5-4ade-958b-ad09e623a1d4" xlink:href="espr-20250630.xsd#espr_SignificantAccountingPoliciesLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_SignificantAccountingPoliciesTable_435e8336-d0c5-411e-9053-aec1d9d79cb7" xlink:href="espr-20250630.xsd#espr_SignificantAccountingPoliciesTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_espr_SignificantAccountingPoliciesLineItems_e07f29ff-4dc5-4ade-958b-ad09e623a1d4" xlink:to="loc_espr_SignificantAccountingPoliciesTable_435e8336-d0c5-411e-9053-aec1d9d79cb7" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ConcentrationRiskByBenchmarkAxis_4af1a8f9-c262-4b4b-b010-057f732d1901" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ConcentrationRiskByBenchmarkAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_espr_SignificantAccountingPoliciesTable_435e8336-d0c5-411e-9053-aec1d9d79cb7" xlink:to="loc_us-gaap_ConcentrationRiskByBenchmarkAxis_4af1a8f9-c262-4b4b-b010-057f732d1901" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ConcentrationRiskBenchmarkDomain_4af1a8f9-c262-4b4b-b010-057f732d1901_default" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ConcentrationRiskBenchmarkDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_ConcentrationRiskByBenchmarkAxis_4af1a8f9-c262-4b4b-b010-057f732d1901" xlink:to="loc_us-gaap_ConcentrationRiskBenchmarkDomain_4af1a8f9-c262-4b4b-b010-057f732d1901_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ConcentrationRiskBenchmarkDomain_fcc9558b-9a63-42dc-a251-085f228584a5" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ConcentrationRiskBenchmarkDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_ConcentrationRiskByBenchmarkAxis_4af1a8f9-c262-4b4b-b010-057f732d1901" xlink:to="loc_us-gaap_ConcentrationRiskBenchmarkDomain_fcc9558b-9a63-42dc-a251-085f228584a5" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_TradeAccountsReceivableMember_3dab403f-075f-4e43-9839-a9027a9d8aef" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_TradeAccountsReceivableMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ConcentrationRiskBenchmarkDomain_fcc9558b-9a63-42dc-a251-085f228584a5" xlink:to="loc_us-gaap_TradeAccountsReceivableMember_3dab403f-075f-4e43-9839-a9027a9d8aef" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SalesRevenueNetMember_a4e190e5-9ddd-4f8e-a21c-3c9cfe5351af" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_SalesRevenueNetMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ConcentrationRiskBenchmarkDomain_fcc9558b-9a63-42dc-a251-085f228584a5" xlink:to="loc_us-gaap_SalesRevenueNetMember_a4e190e5-9ddd-4f8e-a21c-3c9cfe5351af" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ConcentrationRiskByTypeAxis_79e65a98-ab8b-4e32-b8a1-48ed120c242f" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ConcentrationRiskByTypeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_espr_SignificantAccountingPoliciesTable_435e8336-d0c5-411e-9053-aec1d9d79cb7" xlink:to="loc_us-gaap_ConcentrationRiskByTypeAxis_79e65a98-ab8b-4e32-b8a1-48ed120c242f" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ConcentrationRiskTypeDomain_79e65a98-ab8b-4e32-b8a1-48ed120c242f_default" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ConcentrationRiskTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_ConcentrationRiskByTypeAxis_79e65a98-ab8b-4e32-b8a1-48ed120c242f" xlink:to="loc_us-gaap_ConcentrationRiskTypeDomain_79e65a98-ab8b-4e32-b8a1-48ed120c242f_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ConcentrationRiskTypeDomain_f6bf61cc-73fa-432b-8c14-3295fbbc22c2" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ConcentrationRiskTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_ConcentrationRiskByTypeAxis_79e65a98-ab8b-4e32-b8a1-48ed120c242f" xlink:to="loc_us-gaap_ConcentrationRiskTypeDomain_f6bf61cc-73fa-432b-8c14-3295fbbc22c2" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CustomerConcentrationRiskMember_5b49551d-6e8c-4f8f-bcad-6937d2c10bb2" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_CustomerConcentrationRiskMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ConcentrationRiskTypeDomain_f6bf61cc-73fa-432b-8c14-3295fbbc22c2" xlink:to="loc_us-gaap_CustomerConcentrationRiskMember_5b49551d-6e8c-4f8f-bcad-6937d2c10bb2" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_AccountsReceivableRisksMember_e7c15eea-c5aa-4de4-bc1a-234263507b95" xlink:href="espr-20250630.xsd#espr_AccountsReceivableRisksMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ConcentrationRiskTypeDomain_f6bf61cc-73fa-432b-8c14-3295fbbc22c2" xlink:to="loc_espr_AccountsReceivableRisksMember_e7c15eea-c5aa-4de4-bc1a-234263507b95" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ProductConcentrationRiskMember_3b32b4a6-4d85-435b-a51f-703568810755" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ProductConcentrationRiskMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ConcentrationRiskTypeDomain_f6bf61cc-73fa-432b-8c14-3295fbbc22c2" xlink:to="loc_us-gaap_ProductConcentrationRiskMember_3b32b4a6-4d85-435b-a51f-703568810755" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductOrServiceAxis_d91abfe2-4e09-4dc0-841f-e8283e33398c" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_ProductOrServiceAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_espr_SignificantAccountingPoliciesTable_435e8336-d0c5-411e-9053-aec1d9d79cb7" xlink:to="loc_srt_ProductOrServiceAxis_d91abfe2-4e09-4dc0-841f-e8283e33398c" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductsAndServicesDomain_d91abfe2-4e09-4dc0-841f-e8283e33398c_default" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_ProductsAndServicesDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_ProductOrServiceAxis_d91abfe2-4e09-4dc0-841f-e8283e33398c" xlink:to="loc_srt_ProductsAndServicesDomain_d91abfe2-4e09-4dc0-841f-e8283e33398c_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductsAndServicesDomain_36e61e62-bacf-4c6e-9d39-0eb174a8dc0e" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_ProductsAndServicesDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_ProductOrServiceAxis_d91abfe2-4e09-4dc0-841f-e8283e33398c" xlink:to="loc_srt_ProductsAndServicesDomain_36e61e62-bacf-4c6e-9d39-0eb174a8dc0e" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ProductMember_485a2c71-a99d-4647-8b9a-1e52de5ec5bb" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ProductMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ProductsAndServicesDomain_36e61e62-bacf-4c6e-9d39-0eb174a8dc0e" xlink:to="loc_us-gaap_ProductMember_485a2c71-a99d-4647-8b9a-1e52de5ec5bb" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_MajorCustomersAxis_3fb8fdbb-d06a-465c-8dd7-1bcd33c844a6" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_MajorCustomersAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_espr_SignificantAccountingPoliciesTable_435e8336-d0c5-411e-9053-aec1d9d79cb7" xlink:to="loc_srt_MajorCustomersAxis_3fb8fdbb-d06a-465c-8dd7-1bcd33c844a6" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_NameOfMajorCustomerDomain_3fb8fdbb-d06a-465c-8dd7-1bcd33c844a6_default" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_NameOfMajorCustomerDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_MajorCustomersAxis_3fb8fdbb-d06a-465c-8dd7-1bcd33c844a6" xlink:to="loc_srt_NameOfMajorCustomerDomain_3fb8fdbb-d06a-465c-8dd7-1bcd33c844a6_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_NameOfMajorCustomerDomain_07c191ec-7206-44b0-a112-4e7a59ddf469" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_NameOfMajorCustomerDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_MajorCustomersAxis_3fb8fdbb-d06a-465c-8dd7-1bcd33c844a6" xlink:to="loc_srt_NameOfMajorCustomerDomain_07c191ec-7206-44b0-a112-4e7a59ddf469" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_ThreeLargestCustomersMember_d2841a02-05ae-4311-bd24-d7e7a2b9de60" xlink:href="espr-20250630.xsd#espr_ThreeLargestCustomersMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_NameOfMajorCustomerDomain_07c191ec-7206-44b0-a112-4e7a59ddf469" xlink:to="loc_espr_ThreeLargestCustomersMember_d2841a02-05ae-4311-bd24-d7e7a2b9de60" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_NumberOfOperatingSegments_66a3cdff-3fed-4e48-84df-bf49f5ac2a13" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_NumberOfOperatingSegments"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_espr_SignificantAccountingPoliciesLineItems_e07f29ff-4dc5-4ade-958b-ad09e623a1d4" xlink:to="loc_us-gaap_NumberOfOperatingSegments_66a3cdff-3fed-4e48-84df-bf49f5ac2a13" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_ConcentrationRiskNumberOfCustomers_ee9f767c-fd8d-4742-8150-85d3a819e8a2" xlink:href="espr-20250630.xsd#espr_ConcentrationRiskNumberOfCustomers"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_espr_SignificantAccountingPoliciesLineItems_e07f29ff-4dc5-4ade-958b-ad09e623a1d4" xlink:to="loc_espr_ConcentrationRiskNumberOfCustomers_ee9f767c-fd8d-4742-8150-85d3a819e8a2" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ConcentrationRiskPercentage1_56ede99c-c2db-494a-8a50-df4ce5d281fb" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ConcentrationRiskPercentage1"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_espr_SignificantAccountingPoliciesLineItems_e07f29ff-4dc5-4ade-958b-ad09e623a1d4" xlink:to="loc_us-gaap_ConcentrationRiskPercentage1_56ede99c-c2db-494a-8a50-df4ce5d281fb" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_NumberOfSourcesOfRevenue_79778c25-e0bd-47da-8464-7ce4cbf050a4" xlink:href="espr-20250630.xsd#espr_NumberOfSourcesOfRevenue"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_espr_SignificantAccountingPoliciesLineItems_e07f29ff-4dc5-4ade-958b-ad09e623a1d4" xlink:to="loc_espr_NumberOfSourcesOfRevenue_79778c25-e0bd-47da-8464-7ce4cbf050a4" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax_85b41976-8e75-482a-84c4-b2e12447180f" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_espr_SignificantAccountingPoliciesLineItems_e07f29ff-4dc5-4ade-958b-ad09e623a1d4" xlink:to="loc_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax_85b41976-8e75-482a-84c4-b2e12447180f" xlink:type="arc" order="4"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.esperion.com/role/CollaborationswithThirdPartiesDetails" xlink:type="simple" xlink:href="espr-20250630.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_f852e925-407a-4783-a460-97014b779e6a" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable_fb8c01f3-0f1a-43de-b1a1-863ebb91bb12" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_f852e925-407a-4783-a460-97014b779e6a" xlink:to="loc_us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable_fb8c01f3-0f1a-43de-b1a1-863ebb91bb12" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_CounterpartyNameAxis_0a2b2152-30bc-4a34-bb2e-cc7c139e72b1" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_CounterpartyNameAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable_fb8c01f3-0f1a-43de-b1a1-863ebb91bb12" xlink:to="loc_srt_CounterpartyNameAxis_0a2b2152-30bc-4a34-bb2e-cc7c139e72b1" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RepurchaseAgreementCounterpartyNameDomain_0a2b2152-30bc-4a34-bb2e-cc7c139e72b1_default" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_RepurchaseAgreementCounterpartyNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_CounterpartyNameAxis_0a2b2152-30bc-4a34-bb2e-cc7c139e72b1" xlink:to="loc_srt_RepurchaseAgreementCounterpartyNameDomain_0a2b2152-30bc-4a34-bb2e-cc7c139e72b1_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RepurchaseAgreementCounterpartyNameDomain_b392fba5-4011-4c95-8931-7e0f8beddf80" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_RepurchaseAgreementCounterpartyNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_CounterpartyNameAxis_0a2b2152-30bc-4a34-bb2e-cc7c139e72b1" xlink:to="loc_srt_RepurchaseAgreementCounterpartyNameDomain_b392fba5-4011-4c95-8931-7e0f8beddf80" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_DaiichiSankyoEuropeGmbhMember_234b10c6-e6e4-45d9-ba76-f7e6c675c888" xlink:href="espr-20250630.xsd#espr_DaiichiSankyoEuropeGmbhMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_RepurchaseAgreementCounterpartyNameDomain_b392fba5-4011-4c95-8931-7e0f8beddf80" xlink:to="loc_espr_DaiichiSankyoEuropeGmbhMember_234b10c6-e6e4-45d9-ba76-f7e6c675c888" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_OtsukaPharmaceuticalCoLtdMember_1d3d7ea1-dc5a-45dd-8f75-6ba759356407" xlink:href="espr-20250630.xsd#espr_OtsukaPharmaceuticalCoLtdMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_RepurchaseAgreementCounterpartyNameDomain_b392fba5-4011-4c95-8931-7e0f8beddf80" xlink:to="loc_espr_OtsukaPharmaceuticalCoLtdMember_1d3d7ea1-dc5a-45dd-8f75-6ba759356407" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_DaiichiSankyoCoLtdMember_72936471-3da5-46f3-a3e2-492a34dca08e" xlink:href="espr-20250630.xsd#espr_DaiichiSankyoCoLtdMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_RepurchaseAgreementCounterpartyNameDomain_b392fba5-4011-4c95-8931-7e0f8beddf80" xlink:to="loc_espr_DaiichiSankyoCoLtdMember_72936471-3da5-46f3-a3e2-492a34dca08e" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_SeqirusPtyLtdMember_2b1497a1-def8-44b3-9580-679b3a272bd1" xlink:href="espr-20250630.xsd#espr_SeqirusPtyLtdMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_RepurchaseAgreementCounterpartyNameDomain_b392fba5-4011-4c95-8931-7e0f8beddf80" xlink:to="loc_espr_SeqirusPtyLtdMember_2b1497a1-def8-44b3-9580-679b3a272bd1" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_HLSTherapeuticsMember_dc351356-c26f-4c57-9d18-58ad6ddc217c" xlink:href="espr-20250630.xsd#espr_HLSTherapeuticsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_RepurchaseAgreementCounterpartyNameDomain_b392fba5-4011-4c95-8931-7e0f8beddf80" xlink:to="loc_espr_HLSTherapeuticsMember_dc351356-c26f-4c57-9d18-58ad6ddc217c" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_TypeOfArrangementAxis_a85d1e42-7b03-4c8a-beab-b86db76d1eff" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_TypeOfArrangementAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable_fb8c01f3-0f1a-43de-b1a1-863ebb91bb12" xlink:to="loc_us-gaap_TypeOfArrangementAxis_a85d1e42-7b03-4c8a-beab-b86db76d1eff" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ArrangementsAndNonarrangementTransactionsMember_a85d1e42-7b03-4c8a-beab-b86db76d1eff_default" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ArrangementsAndNonarrangementTransactionsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_TypeOfArrangementAxis_a85d1e42-7b03-4c8a-beab-b86db76d1eff" xlink:to="loc_us-gaap_ArrangementsAndNonarrangementTransactionsMember_a85d1e42-7b03-4c8a-beab-b86db76d1eff_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ArrangementsAndNonarrangementTransactionsMember_425f7024-44ab-40a1-8416-12064dd2173a" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ArrangementsAndNonarrangementTransactionsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_TypeOfArrangementAxis_a85d1e42-7b03-4c8a-beab-b86db76d1eff" xlink:to="loc_us-gaap_ArrangementsAndNonarrangementTransactionsMember_425f7024-44ab-40a1-8416-12064dd2173a" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CollaborativeArrangementMember_02ec7024-fbd5-4be3-afd6-5ad9ffdc9dab" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_CollaborativeArrangementMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ArrangementsAndNonarrangementTransactionsMember_425f7024-44ab-40a1-8416-12064dd2173a" xlink:to="loc_us-gaap_CollaborativeArrangementMember_02ec7024-fbd5-4be3-afd6-5ad9ffdc9dab" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_ExclusiveDevelopmentalActivitiesMember_15ba94c2-63cc-4755-96cd-a46609e6d090" xlink:href="espr-20250630.xsd#espr_ExclusiveDevelopmentalActivitiesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ArrangementsAndNonarrangementTransactionsMember_425f7024-44ab-40a1-8416-12064dd2173a" xlink:to="loc_espr_ExclusiveDevelopmentalActivitiesMember_15ba94c2-63cc-4755-96cd-a46609e6d090" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RangeAxis_1c9fb586-0a13-4bf2-b8b8-ad8c918d229e" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_RangeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable_fb8c01f3-0f1a-43de-b1a1-863ebb91bb12" xlink:to="loc_srt_RangeAxis_1c9fb586-0a13-4bf2-b8b8-ad8c918d229e" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RangeMember_1c9fb586-0a13-4bf2-b8b8-ad8c918d229e_default" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_RangeMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_RangeAxis_1c9fb586-0a13-4bf2-b8b8-ad8c918d229e" xlink:to="loc_srt_RangeMember_1c9fb586-0a13-4bf2-b8b8-ad8c918d229e_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RangeMember_2abb2a34-c839-4ba5-9893-1c0f59e680fc" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_RangeMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_RangeAxis_1c9fb586-0a13-4bf2-b8b8-ad8c918d229e" xlink:to="loc_srt_RangeMember_2abb2a34-c839-4ba5-9893-1c0f59e680fc" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_MinimumMember_7e789fc4-d96c-49e8-aea8-9aec87285965" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_MinimumMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_RangeMember_2abb2a34-c839-4ba5-9893-1c0f59e680fc" xlink:to="loc_srt_MinimumMember_7e789fc4-d96c-49e8-aea8-9aec87285965" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_MaximumMember_4891644f-2cbc-41f6-b870-cc1cc31c52f4" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_MaximumMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_RangeMember_2abb2a34-c839-4ba5-9893-1c0f59e680fc" xlink:to="loc_srt_MaximumMember_4891644f-2cbc-41f6-b870-cc1cc31c52f4" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductOrServiceAxis_d013c2c7-9999-4973-951e-b11077644ec2" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_ProductOrServiceAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable_fb8c01f3-0f1a-43de-b1a1-863ebb91bb12" xlink:to="loc_srt_ProductOrServiceAxis_d013c2c7-9999-4973-951e-b11077644ec2" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductsAndServicesDomain_d013c2c7-9999-4973-951e-b11077644ec2_default" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_ProductsAndServicesDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_ProductOrServiceAxis_d013c2c7-9999-4973-951e-b11077644ec2" xlink:to="loc_srt_ProductsAndServicesDomain_d013c2c7-9999-4973-951e-b11077644ec2_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductsAndServicesDomain_c58bebd0-cb36-4e88-bad2-2249d5b86c89" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_ProductsAndServicesDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_ProductOrServiceAxis_d013c2c7-9999-4973-951e-b11077644ec2" xlink:to="loc_srt_ProductsAndServicesDomain_c58bebd0-cb36-4e88-bad2-2249d5b86c89" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_RoyaltyRevenueFromDSEAndSaleOfBulkTabletsAndMilestonesReceivedMember_e62a603c-c788-4c21-a05c-4f1621349086" xlink:href="espr-20250630.xsd#espr_RoyaltyRevenueFromDSEAndSaleOfBulkTabletsAndMilestonesReceivedMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ProductsAndServicesDomain_c58bebd0-cb36-4e88-bad2-2249d5b86c89" xlink:to="loc_espr_RoyaltyRevenueFromDSEAndSaleOfBulkTabletsAndMilestonesReceivedMember_e62a603c-c788-4c21-a05c-4f1621349086" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_CollaborationRevenueMember_bb1805ed-f6a3-4e89-8cce-89a6dcc16255" xlink:href="espr-20250630.xsd#espr_CollaborationRevenueMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ProductsAndServicesDomain_c58bebd0-cb36-4e88-bad2-2249d5b86c89" xlink:to="loc_espr_CollaborationRevenueMember_bb1805ed-f6a3-4e89-8cce-89a6dcc16255" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SubsidiarySaleOfStockAxis_121abb50-8201-41f8-891f-67d949d6c0cf" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_SubsidiarySaleOfStockAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable_fb8c01f3-0f1a-43de-b1a1-863ebb91bb12" xlink:to="loc_us-gaap_SubsidiarySaleOfStockAxis_121abb50-8201-41f8-891f-67d949d6c0cf" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SaleOfStockNameOfTransactionDomain_121abb50-8201-41f8-891f-67d949d6c0cf_default" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_SaleOfStockNameOfTransactionDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_SubsidiarySaleOfStockAxis_121abb50-8201-41f8-891f-67d949d6c0cf" xlink:to="loc_us-gaap_SaleOfStockNameOfTransactionDomain_121abb50-8201-41f8-891f-67d949d6c0cf_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SaleOfStockNameOfTransactionDomain_a35bd45b-cb90-4c82-bdca-e49b699b0da6" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_SaleOfStockNameOfTransactionDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_SubsidiarySaleOfStockAxis_121abb50-8201-41f8-891f-67d949d6c0cf" xlink:to="loc_us-gaap_SaleOfStockNameOfTransactionDomain_a35bd45b-cb90-4c82-bdca-e49b699b0da6" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_CommitmentOfferingMember_24d3a6ae-467f-46a2-9cdc-5df1c0e3ed85" xlink:href="espr-20250630.xsd#espr_CommitmentOfferingMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SaleOfStockNameOfTransactionDomain_a35bd45b-cb90-4c82-bdca-e49b699b0da6" xlink:to="loc_espr_CommitmentOfferingMember_24d3a6ae-467f-46a2-9cdc-5df1c0e3ed85" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_UpFrontPayment_fad1e91e-48fe-44d7-9fda-306da4bc044b" xlink:href="espr-20250630.xsd#espr_UpFrontPayment"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_f852e925-407a-4783-a460-97014b779e6a" xlink:to="loc_espr_UpFrontPayment_fad1e91e-48fe-44d7-9fda-306da4bc044b" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_CashPaymentToBeReceivedUponFirstCommercialSales_9bc9babd-7565-4b18-8ad7-1e807240fe87" xlink:href="espr-20250630.xsd#espr_CashPaymentToBeReceivedUponFirstCommercialSales"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_f852e925-407a-4783-a460-97014b779e6a" xlink:to="loc_espr_CashPaymentToBeReceivedUponFirstCommercialSales_9bc9babd-7565-4b18-8ad7-1e807240fe87" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_PercentageOfRoyaltiesToBeReceivedOnNetSales_546416c2-11b5-4a4b-8490-54b2ccd2505c" xlink:href="espr-20250630.xsd#espr_PercentageOfRoyaltiesToBeReceivedOnNetSales"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_f852e925-407a-4783-a460-97014b779e6a" xlink:to="loc_espr_PercentageOfRoyaltiesToBeReceivedOnNetSales_546416c2-11b5-4a4b-8490-54b2ccd2505c" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_SettlementAgreementAggregatePaymentFromPartner_edd03c99-1e01-4cae-95e2-fb02049b2c62" xlink:href="espr-20250630.xsd#espr_SettlementAgreementAggregatePaymentFromPartner"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_f852e925-407a-4783-a460-97014b779e6a" xlink:to="loc_espr_SettlementAgreementAggregatePaymentFromPartner_edd03c99-1e01-4cae-95e2-fb02049b2c62" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_SettlementAgreementAggregateFirstMilestonePaymentFromPartner_c73837ee-2e79-42d9-9249-c487674d224f" xlink:href="espr-20250630.xsd#espr_SettlementAgreementAggregateFirstMilestonePaymentFromPartner"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_f852e925-407a-4783-a460-97014b779e6a" xlink:to="loc_espr_SettlementAgreementAggregateFirstMilestonePaymentFromPartner_c73837ee-2e79-42d9-9249-c487674d224f" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_SettlementAgreementTimeRequiredToPayCashPortionOfSettlement_42e7cb7f-7ca0-4f16-acdd-9285b15e8e80" xlink:href="espr-20250630.xsd#espr_SettlementAgreementTimeRequiredToPayCashPortionOfSettlement"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_f852e925-407a-4783-a460-97014b779e6a" xlink:to="loc_espr_SettlementAgreementTimeRequiredToPayCashPortionOfSettlement_42e7cb7f-7ca0-4f16-acdd-9285b15e8e80" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_SettlementAgreementAggregateSecondMilestonePaymentFromPartner_998d5b66-9c09-4ebc-8ddc-0a9d4e0f345d" xlink:href="espr-20250630.xsd#espr_SettlementAgreementAggregateSecondMilestonePaymentFromPartner"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_f852e925-407a-4783-a460-97014b779e6a" xlink:to="loc_espr_SettlementAgreementAggregateSecondMilestonePaymentFromPartner_998d5b66-9c09-4ebc-8ddc-0a9d4e0f345d" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_ContractWithCustomerLiabilityOneTimePaymentCurrent_97c0b792-7473-4101-a8b1-1108a3e38711" xlink:href="espr-20250630.xsd#espr_ContractWithCustomerLiabilityOneTimePaymentCurrent"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_f852e925-407a-4783-a460-97014b779e6a" xlink:to="loc_espr_ContractWithCustomerLiabilityOneTimePaymentCurrent_97c0b792-7473-4101-a8b1-1108a3e38711" xlink:type="arc" order="7"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_RoyaltyRateOnNetSales_1535c265-5f01-417a-b0ae-5cf6ade0a5a2" xlink:href="espr-20250630.xsd#espr_RoyaltyRateOnNetSales"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_f852e925-407a-4783-a460-97014b779e6a" xlink:to="loc_espr_RoyaltyRateOnNetSales_1535c265-5f01-417a-b0ae-5cf6ade0a5a2" xlink:type="arc" order="8"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax_1e62e66d-c871-419a-b02c-5c0923ceafde" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_f852e925-407a-4783-a460-97014b779e6a" xlink:to="loc_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax_1e62e66d-c871-419a-b02c-5c0923ceafde" xlink:type="arc" order="9"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_AggregateAmountOfPotentialFutureRevenueTotalDevelopmentAndSalesMilestones_6e1e5bfc-da66-488d-b664-0b5c5e6dd2b4" xlink:href="espr-20250630.xsd#espr_AggregateAmountOfPotentialFutureRevenueTotalDevelopmentAndSalesMilestones"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_f852e925-407a-4783-a460-97014b779e6a" xlink:to="loc_espr_AggregateAmountOfPotentialFutureRevenueTotalDevelopmentAndSalesMilestones_6e1e5bfc-da66-488d-b664-0b5c5e6dd2b4" xlink:type="arc" order="10"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_ProceedsFromMilestonePayment_f320c6b2-7120-48c0-b618-c943732a0b3e" xlink:href="espr-20250630.xsd#espr_ProceedsFromMilestonePayment"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_f852e925-407a-4783-a460-97014b779e6a" xlink:to="loc_espr_ProceedsFromMilestonePayment_f320c6b2-7120-48c0-b618-c943732a0b3e" xlink:type="arc" order="11"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_FuturePaymentMilestoneFirstSubmissionOfJapaneseNewDrugApplicationOtsukaTerritory_8ac06bb0-d1b8-473c-aa84-80d102a00bd1" xlink:href="espr-20250630.xsd#espr_FuturePaymentMilestoneFirstSubmissionOfJapaneseNewDrugApplicationOtsukaTerritory"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_f852e925-407a-4783-a460-97014b779e6a" xlink:to="loc_espr_FuturePaymentMilestoneFirstSubmissionOfJapaneseNewDrugApplicationOtsukaTerritory_8ac06bb0-d1b8-473c-aa84-80d102a00bd1" xlink:type="arc" order="12"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_FuturePaymentMilestoneFirstNationalHealthInsurancePriceListingOtsukaTerritory_6c2e670e-c421-4a78-997e-605c3e388365" xlink:href="espr-20250630.xsd#espr_FuturePaymentMilestoneFirstNationalHealthInsurancePriceListingOtsukaTerritory"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_f852e925-407a-4783-a460-97014b779e6a" xlink:to="loc_espr_FuturePaymentMilestoneFirstNationalHealthInsurancePriceListingOtsukaTerritory_6c2e670e-c421-4a78-997e-605c3e388365" xlink:type="arc" order="13"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_FuturePaymentMilestoneAchievementOfDrugTrialOutcomesStudies_b6832cbb-2ea4-40d1-89bb-4359f7a8eb50" xlink:href="espr-20250630.xsd#espr_FuturePaymentMilestoneAchievementOfDrugTrialOutcomesStudies"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_f852e925-407a-4783-a460-97014b779e6a" xlink:to="loc_espr_FuturePaymentMilestoneAchievementOfDrugTrialOutcomesStudies_b6832cbb-2ea4-40d1-89bb-4359f7a8eb50" xlink:type="arc" order="14"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_FuturePaymentMilestoneSalesMilestones_a4cb8981-f73d-4a6a-9104-647407739c8f" xlink:href="espr-20250630.xsd#espr_FuturePaymentMilestoneSalesMilestones"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_f852e925-407a-4783-a460-97014b779e6a" xlink:to="loc_espr_FuturePaymentMilestoneSalesMilestones_a4cb8981-f73d-4a6a-9104-647407739c8f" xlink:type="arc" order="15"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_FutureUpFrontPayment_600c3574-717d-4605-89e8-294bceeba8bb" xlink:href="espr-20250630.xsd#espr_FutureUpFrontPayment"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_f852e925-407a-4783-a460-97014b779e6a" xlink:to="loc_espr_FutureUpFrontPayment_600c3574-717d-4605-89e8-294bceeba8bb" xlink:type="arc" order="16"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_CashPaymentToBeReceivedUponCertainCommercialMilestones_f614f16e-37e7-4788-8fdc-063a0e938ca9" xlink:href="espr-20250630.xsd#espr_CashPaymentToBeReceivedUponCertainCommercialMilestones"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_f852e925-407a-4783-a460-97014b779e6a" xlink:to="loc_espr_CashPaymentToBeReceivedUponCertainCommercialMilestones_f614f16e-37e7-4788-8fdc-063a0e938ca9" xlink:type="arc" order="17"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.esperion.com/role/CashEquivalentsSummaryofCashEquivalentsandShortTermInvestmentsDetails" xlink:type="simple" xlink:href="espr-20250630.xsd#CashEquivalentsSummaryofCashEquivalentsandShortTermInvestmentsDetails"/>
  <link:definitionLink xlink:role="http://www.esperion.com/role/CashEquivalentsSummaryofCashEquivalentsandShortTermInvestmentsDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfAvailableForSaleSecuritiesLineItems_ede80138-3eec-4fc9-9846-0a01424ae99a" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ScheduleOfAvailableForSaleSecuritiesLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtSecuritiesAvailableForSaleTable_566af799-b120-4a60-8f17-ea050f734c56" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_DebtSecuritiesAvailableForSaleTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_ScheduleOfAvailableForSaleSecuritiesLineItems_ede80138-3eec-4fc9-9846-0a01424ae99a" xlink:to="loc_us-gaap_DebtSecuritiesAvailableForSaleTable_566af799-b120-4a60-8f17-ea050f734c56" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FinancialInstrumentAxis_8f677657-d58b-4518-b446-f21ac806b5ff" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_FinancialInstrumentAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_DebtSecuritiesAvailableForSaleTable_566af799-b120-4a60-8f17-ea050f734c56" xlink:to="loc_us-gaap_FinancialInstrumentAxis_8f677657-d58b-4518-b446-f21ac806b5ff" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_8f677657-d58b-4518-b446-f21ac806b5ff_default" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_FinancialInstrumentAxis_8f677657-d58b-4518-b446-f21ac806b5ff" xlink:to="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_8f677657-d58b-4518-b446-f21ac806b5ff_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_f19a44cc-ab7c-4660-8b39-a748b04d8444" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_FinancialInstrumentAxis_8f677657-d58b-4518-b446-f21ac806b5ff" xlink:to="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_f19a44cc-ab7c-4660-8b39-a748b04d8444" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_MoneyMarketFundsMember_54b63941-03f9-4cb6-bf12-b1b8c6fdf3fd" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_MoneyMarketFundsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_f19a44cc-ab7c-4660-8b39-a748b04d8444" xlink:to="loc_us-gaap_MoneyMarketFundsMember_54b63941-03f9-4cb6-bf12-b1b8c6fdf3fd" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CertificatesOfDepositMember_88cc9837-6407-4de1-ac17-3127cca2f624" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_CertificatesOfDepositMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_f19a44cc-ab7c-4660-8b39-a748b04d8444" xlink:to="loc_us-gaap_CertificatesOfDepositMember_88cc9837-6407-4de1-ac17-3127cca2f624" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_BalanceSheetLocationAxis_958bf7d0-6172-4b46-836a-e1a4eda7ad19" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_BalanceSheetLocationAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_DebtSecuritiesAvailableForSaleTable_566af799-b120-4a60-8f17-ea050f734c56" xlink:to="loc_us-gaap_BalanceSheetLocationAxis_958bf7d0-6172-4b46-836a-e1a4eda7ad19" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_BalanceSheetLocationDomain_958bf7d0-6172-4b46-836a-e1a4eda7ad19_default" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_BalanceSheetLocationDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_BalanceSheetLocationAxis_958bf7d0-6172-4b46-836a-e1a4eda7ad19" xlink:to="loc_us-gaap_BalanceSheetLocationDomain_958bf7d0-6172-4b46-836a-e1a4eda7ad19_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_BalanceSheetLocationDomain_27bf49a7-50b5-4472-b236-b2daba3955d9" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_BalanceSheetLocationDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_BalanceSheetLocationAxis_958bf7d0-6172-4b46-836a-e1a4eda7ad19" xlink:to="loc_us-gaap_BalanceSheetLocationDomain_27bf49a7-50b5-4472-b236-b2daba3955d9" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CashEquivalentsMember_e70a8543-eddf-4d3b-8dbd-1e306669af51" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_CashEquivalentsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_BalanceSheetLocationDomain_27bf49a7-50b5-4472-b236-b2daba3955d9" xlink:to="loc_us-gaap_CashEquivalentsMember_e70a8543-eddf-4d3b-8dbd-1e306669af51" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AvailableForSaleDebtSecuritiesAmortizedCostBasis_7151ec18-f109-4105-aae1-be0fe0073b58" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_AvailableForSaleDebtSecuritiesAmortizedCostBasis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ScheduleOfAvailableForSaleSecuritiesLineItems_ede80138-3eec-4fc9-9846-0a01424ae99a" xlink:to="loc_us-gaap_AvailableForSaleDebtSecuritiesAmortizedCostBasis_7151ec18-f109-4105-aae1-be0fe0073b58" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax_62617280-ed4b-4004-9b89-53bbb93a2830" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ScheduleOfAvailableForSaleSecuritiesLineItems_ede80138-3eec-4fc9-9846-0a01424ae99a" xlink:to="loc_us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax_62617280-ed4b-4004-9b89-53bbb93a2830" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax_7205605a-7888-41a7-8ac6-fe5bcb6655da" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ScheduleOfAvailableForSaleSecuritiesLineItems_ede80138-3eec-4fc9-9846-0a01424ae99a" xlink:to="loc_us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax_7205605a-7888-41a7-8ac6-fe5bcb6655da" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AvailableForSaleSecuritiesDebtSecurities_afd10d2d-b1fe-4f0d-af99-109551cae900" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_AvailableForSaleSecuritiesDebtSecurities"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ScheduleOfAvailableForSaleSecuritiesLineItems_ede80138-3eec-4fc9-9846-0a01424ae99a" xlink:to="loc_us-gaap_AvailableForSaleSecuritiesDebtSecurities_afd10d2d-b1fe-4f0d-af99-109551cae900" xlink:type="arc" order="3"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.esperion.com/role/CashEquivalentsNarrativeDetails" xlink:type="simple" xlink:href="espr-20250630.xsd#CashEquivalentsNarrativeDetails"/>
  <link:definitionLink xlink:role="http://www.esperion.com/role/CashEquivalentsNarrativeDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfAvailableForSaleSecuritiesLineItems_3bccbbff-81ea-4ce4-9fb5-61a235409cf8" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ScheduleOfAvailableForSaleSecuritiesLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtSecuritiesAvailableForSaleTable_2d4706b7-ad5b-42cb-a9a8-38ef7f6b1e48" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_DebtSecuritiesAvailableForSaleTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_ScheduleOfAvailableForSaleSecuritiesLineItems_3bccbbff-81ea-4ce4-9fb5-61a235409cf8" xlink:to="loc_us-gaap_DebtSecuritiesAvailableForSaleTable_2d4706b7-ad5b-42cb-a9a8-38ef7f6b1e48" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncomeStatementLocationAxis_825d2bcf-825b-47b2-8fdd-f15bccba1b3a" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_IncomeStatementLocationAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_DebtSecuritiesAvailableForSaleTable_2d4706b7-ad5b-42cb-a9a8-38ef7f6b1e48" xlink:to="loc_us-gaap_IncomeStatementLocationAxis_825d2bcf-825b-47b2-8fdd-f15bccba1b3a" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncomeStatementLocationDomain_825d2bcf-825b-47b2-8fdd-f15bccba1b3a_default" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_IncomeStatementLocationDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_IncomeStatementLocationAxis_825d2bcf-825b-47b2-8fdd-f15bccba1b3a" xlink:to="loc_us-gaap_IncomeStatementLocationDomain_825d2bcf-825b-47b2-8fdd-f15bccba1b3a_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncomeStatementLocationDomain_bb122a72-2d29-45b5-b8a3-cce1c5ea2c56" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_IncomeStatementLocationDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_IncomeStatementLocationAxis_825d2bcf-825b-47b2-8fdd-f15bccba1b3a" xlink:to="loc_us-gaap_IncomeStatementLocationDomain_bb122a72-2d29-45b5-b8a3-cce1c5ea2c56" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OtherNonoperatingIncomeExpenseMember_ee40ebbc-b2ab-4146-bcd3-db6d6efd0e6c" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_OtherNonoperatingIncomeExpenseMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncomeStatementLocationDomain_bb122a72-2d29-45b5-b8a3-cce1c5ea2c56" xlink:to="loc_us-gaap_OtherNonoperatingIncomeExpenseMember_ee40ebbc-b2ab-4146-bcd3-db6d6efd0e6c" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ReclassificationOutOfAccumulatedOtherComprehensiveIncomeAxis_c7aec655-b742-4d94-8fb3-e401c82a1433" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ReclassificationOutOfAccumulatedOtherComprehensiveIncomeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_DebtSecuritiesAvailableForSaleTable_2d4706b7-ad5b-42cb-a9a8-38ef7f6b1e48" xlink:to="loc_us-gaap_ReclassificationOutOfAccumulatedOtherComprehensiveIncomeAxis_c7aec655-b742-4d94-8fb3-e401c82a1433" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ReclassificationOutOfAccumulatedOtherComprehensiveIncomeDomain_c7aec655-b742-4d94-8fb3-e401c82a1433_default" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ReclassificationOutOfAccumulatedOtherComprehensiveIncomeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_ReclassificationOutOfAccumulatedOtherComprehensiveIncomeAxis_c7aec655-b742-4d94-8fb3-e401c82a1433" xlink:to="loc_us-gaap_ReclassificationOutOfAccumulatedOtherComprehensiveIncomeDomain_c7aec655-b742-4d94-8fb3-e401c82a1433_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ReclassificationOutOfAccumulatedOtherComprehensiveIncomeDomain_bc2c4d54-acf6-4469-a84c-349654478b2c" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ReclassificationOutOfAccumulatedOtherComprehensiveIncomeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_ReclassificationOutOfAccumulatedOtherComprehensiveIncomeAxis_c7aec655-b742-4d94-8fb3-e401c82a1433" xlink:to="loc_us-gaap_ReclassificationOutOfAccumulatedOtherComprehensiveIncomeDomain_bc2c4d54-acf6-4469-a84c-349654478b2c" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ReclassificationOutOfAccumulatedOtherComprehensiveIncomeMember_80d632d9-674a-4e3a-b7ce-cef9a70e6efe" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ReclassificationOutOfAccumulatedOtherComprehensiveIncomeMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ReclassificationOutOfAccumulatedOtherComprehensiveIncomeDomain_bc2c4d54-acf6-4469-a84c-349654478b2c" xlink:to="loc_us-gaap_ReclassificationOutOfAccumulatedOtherComprehensiveIncomeMember_80d632d9-674a-4e3a-b7ce-cef9a70e6efe" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_InvestmentIncomeInterest_e32ea7ed-0eba-43e4-ab23-bd614934b0a6" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_InvestmentIncomeInterest"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ScheduleOfAvailableForSaleSecuritiesLineItems_3bccbbff-81ea-4ce4-9fb5-61a235409cf8" xlink:to="loc_us-gaap_InvestmentIncomeInterest_e32ea7ed-0eba-43e4-ab23-bd614934b0a6" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AccretionAmortizationOfDiscountsAndPremiumsInvestments_52382d29-175a-45b4-8ef3-461c06a49f89" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_AccretionAmortizationOfDiscountsAndPremiumsInvestments"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ScheduleOfAvailableForSaleSecuritiesLineItems_3bccbbff-81ea-4ce4-9fb5-61a235409cf8" xlink:to="loc_us-gaap_AccretionAmortizationOfDiscountsAndPremiumsInvestments_52382d29-175a-45b4-8ef3-461c06a49f89" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OtherNonoperatingIncomeExpense_cab6a4a5-5117-4d04-b3ba-b8b41af02414" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_OtherNonoperatingIncomeExpense"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ScheduleOfAvailableForSaleSecuritiesLineItems_3bccbbff-81ea-4ce4-9fb5-61a235409cf8" xlink:to="loc_us-gaap_OtherNonoperatingIncomeExpense_cab6a4a5-5117-4d04-b3ba-b8b41af02414" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtSecuritiesAvailableForSaleAllowanceForCreditLoss_a6a9c010-a6e6-416e-971b-7d6c17abc220" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_DebtSecuritiesAvailableForSaleAllowanceForCreditLoss"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ScheduleOfAvailableForSaleSecuritiesLineItems_3bccbbff-81ea-4ce4-9fb5-61a235409cf8" xlink:to="loc_us-gaap_DebtSecuritiesAvailableForSaleAllowanceForCreditLoss_a6a9c010-a6e6-416e-971b-7d6c17abc220" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AccruedInvestmentIncomeReceivable_04fc3fa4-62ae-4eef-ac83-bd64a8a66df4" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_AccruedInvestmentIncomeReceivable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ScheduleOfAvailableForSaleSecuritiesLineItems_3bccbbff-81ea-4ce4-9fb5-61a235409cf8" xlink:to="loc_us-gaap_AccruedInvestmentIncomeReceivable_04fc3fa4-62ae-4eef-ac83-bd64a8a66df4" xlink:type="arc" order="4"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.esperion.com/role/FairValueMeasurementsDetails" xlink:type="simple" xlink:href="espr-20250630.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_40737bce-a325-4668-b855-403ba6337858" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable_515ad5b5-a6a6-4fd4-bbd1-a4083370d645" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems_40737bce-a325-4668-b855-403ba6337858" xlink:to="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable_515ad5b5-a6a6-4fd4-bbd1-a4083370d645" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueByMeasurementFrequencyAxis_6b04ad98-e88c-4971-8c11-017b8b93c7a1" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_FairValueByMeasurementFrequencyAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable_515ad5b5-a6a6-4fd4-bbd1-a4083370d645" xlink:to="loc_us-gaap_FairValueByMeasurementFrequencyAxis_6b04ad98-e88c-4971-8c11-017b8b93c7a1" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueMeasurementFrequencyDomain_6b04ad98-e88c-4971-8c11-017b8b93c7a1_default" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_FairValueMeasurementFrequencyDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_FairValueByMeasurementFrequencyAxis_6b04ad98-e88c-4971-8c11-017b8b93c7a1" xlink:to="loc_us-gaap_FairValueMeasurementFrequencyDomain_6b04ad98-e88c-4971-8c11-017b8b93c7a1_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueMeasurementFrequencyDomain_626e42c9-d3d9-4b8c-b7c1-56f65f55faf5" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_FairValueMeasurementFrequencyDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_FairValueByMeasurementFrequencyAxis_6b04ad98-e88c-4971-8c11-017b8b93c7a1" xlink:to="loc_us-gaap_FairValueMeasurementFrequencyDomain_626e42c9-d3d9-4b8c-b7c1-56f65f55faf5" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueMeasurementsRecurringMember_0502ca1f-e95f-46cc-85db-eaf0a3547ebb" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_FairValueMeasurementsRecurringMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FairValueMeasurementFrequencyDomain_626e42c9-d3d9-4b8c-b7c1-56f65f55faf5" xlink:to="loc_us-gaap_FairValueMeasurementsRecurringMember_0502ca1f-e95f-46cc-85db-eaf0a3547ebb" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueByFairValueHierarchyLevelAxis_6c08d3e3-a997-400e-81c8-e1b6406daebb" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_FairValueByFairValueHierarchyLevelAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable_515ad5b5-a6a6-4fd4-bbd1-a4083370d645" xlink:to="loc_us-gaap_FairValueByFairValueHierarchyLevelAxis_6c08d3e3-a997-400e-81c8-e1b6406daebb" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueMeasurementsFairValueHierarchyDomain_6c08d3e3-a997-400e-81c8-e1b6406daebb_default" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_FairValueMeasurementsFairValueHierarchyDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_FairValueByFairValueHierarchyLevelAxis_6c08d3e3-a997-400e-81c8-e1b6406daebb" xlink:to="loc_us-gaap_FairValueMeasurementsFairValueHierarchyDomain_6c08d3e3-a997-400e-81c8-e1b6406daebb_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueMeasurementsFairValueHierarchyDomain_e6dfaa9b-6409-44ab-a8d0-66dc3d3c0215" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_FairValueMeasurementsFairValueHierarchyDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_FairValueByFairValueHierarchyLevelAxis_6c08d3e3-a997-400e-81c8-e1b6406daebb" xlink:to="loc_us-gaap_FairValueMeasurementsFairValueHierarchyDomain_e6dfaa9b-6409-44ab-a8d0-66dc3d3c0215" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueInputsLevel1Member_f5df0e43-4913-4d47-9e85-8d921eb0dbe5" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_FairValueInputsLevel1Member"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FairValueMeasurementsFairValueHierarchyDomain_e6dfaa9b-6409-44ab-a8d0-66dc3d3c0215" xlink:to="loc_us-gaap_FairValueInputsLevel1Member_f5df0e43-4913-4d47-9e85-8d921eb0dbe5" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueInputsLevel2Member_f2d05e67-3e63-4cfc-a874-728fd5fc3848" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_FairValueInputsLevel2Member"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FairValueMeasurementsFairValueHierarchyDomain_e6dfaa9b-6409-44ab-a8d0-66dc3d3c0215" xlink:to="loc_us-gaap_FairValueInputsLevel2Member_f2d05e67-3e63-4cfc-a874-728fd5fc3848" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueInputsLevel3Member_113f6441-ca55-4656-8b7f-6f843ef92f12" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_FairValueInputsLevel3Member"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FairValueMeasurementsFairValueHierarchyDomain_e6dfaa9b-6409-44ab-a8d0-66dc3d3c0215" xlink:to="loc_us-gaap_FairValueInputsLevel3Member_113f6441-ca55-4656-8b7f-6f843ef92f12" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FinancialInstrumentAxis_8f9e866e-942d-4ca5-b5df-14d5609ef745" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_FinancialInstrumentAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable_515ad5b5-a6a6-4fd4-bbd1-a4083370d645" xlink:to="loc_us-gaap_FinancialInstrumentAxis_8f9e866e-942d-4ca5-b5df-14d5609ef745" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_8f9e866e-942d-4ca5-b5df-14d5609ef745_default" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_FinancialInstrumentAxis_8f9e866e-942d-4ca5-b5df-14d5609ef745" xlink:to="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_8f9e866e-942d-4ca5-b5df-14d5609ef745_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_ca5dd3a8-cd63-4ab1-9c1a-70ed713d8b88" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_FinancialInstrumentAxis_8f9e866e-942d-4ca5-b5df-14d5609ef745" xlink:to="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_ca5dd3a8-cd63-4ab1-9c1a-70ed713d8b88" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_MoneyMarketFundsMember_4f078ad8-3cd4-4765-af24-4377efdcbb44" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_MoneyMarketFundsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_ca5dd3a8-cd63-4ab1-9c1a-70ed713d8b88" xlink:to="loc_us-gaap_MoneyMarketFundsMember_4f078ad8-3cd4-4765-af24-4377efdcbb44" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CertificatesOfDepositMember_865193bd-8331-4176-8ad3-f16edaddea11" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_CertificatesOfDepositMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_ca5dd3a8-cd63-4ab1-9c1a-70ed713d8b88" xlink:to="loc_us-gaap_CertificatesOfDepositMember_865193bd-8331-4176-8ad3-f16edaddea11" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AssetsFairValueDisclosure_216be84a-0f78-4fa4-be8b-dcb19ffd6f26" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_AssetsFairValueDisclosure"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems_40737bce-a325-4668-b855-403ba6337858" xlink:to="loc_us-gaap_AssetsFairValueDisclosure_216be84a-0f78-4fa4-be8b-dcb19ffd6f26" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_FairValueMeasurementAssetTransfersBetweenLevels_52c5c99c-2498-492c-8db1-43c0c7b5cf0c" xlink:href="espr-20250630.xsd#espr_FairValueMeasurementAssetTransfersBetweenLevels"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems_40737bce-a325-4668-b855-403ba6337858" xlink:to="loc_espr_FairValueMeasurementAssetTransfersBetweenLevels_52c5c99c-2498-492c-8db1-43c0c7b5cf0c" xlink:type="arc" order="1"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.esperion.com/role/LiabilityRelatedtotheRevenueInterestPurchaseAgreementNarrativeDetails" xlink:type="simple" xlink:href="espr-20250630.xsd#LiabilityRelatedtotheRevenueInterestPurchaseAgreementNarrativeDetails"/>
  <link:definitionLink xlink:role="http://www.esperion.com/role/LiabilityRelatedtotheRevenueInterestPurchaseAgreementNarrativeDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfAvailableForSaleSecuritiesLineItems_614d3f34-5dd3-4ac8-8e24-d65b886e3ad9" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ScheduleOfAvailableForSaleSecuritiesLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtSecuritiesAvailableForSaleTable_600cd144-18c4-4567-90c8-57e7ffc32352" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_DebtSecuritiesAvailableForSaleTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_ScheduleOfAvailableForSaleSecuritiesLineItems_614d3f34-5dd3-4ac8-8e24-d65b886e3ad9" xlink:to="loc_us-gaap_DebtSecuritiesAvailableForSaleTable_600cd144-18c4-4567-90c8-57e7ffc32352" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_TypeOfArrangementAxis_5e801193-7a09-44de-b9bc-c3400ac2cb6b" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_TypeOfArrangementAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_DebtSecuritiesAvailableForSaleTable_600cd144-18c4-4567-90c8-57e7ffc32352" xlink:to="loc_us-gaap_TypeOfArrangementAxis_5e801193-7a09-44de-b9bc-c3400ac2cb6b" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ArrangementsAndNonarrangementTransactionsMember_5e801193-7a09-44de-b9bc-c3400ac2cb6b_default" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ArrangementsAndNonarrangementTransactionsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_TypeOfArrangementAxis_5e801193-7a09-44de-b9bc-c3400ac2cb6b" xlink:to="loc_us-gaap_ArrangementsAndNonarrangementTransactionsMember_5e801193-7a09-44de-b9bc-c3400ac2cb6b_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ArrangementsAndNonarrangementTransactionsMember_56fa096c-1eca-4d52-8086-5e0743a4682c" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ArrangementsAndNonarrangementTransactionsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_TypeOfArrangementAxis_5e801193-7a09-44de-b9bc-c3400ac2cb6b" xlink:to="loc_us-gaap_ArrangementsAndNonarrangementTransactionsMember_56fa096c-1eca-4d52-8086-5e0743a4682c" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_RevenueInterestPurchaseAgreementMember_612bf009-6d04-4c99-935c-adac39a8712a" xlink:href="espr-20250630.xsd#espr_RevenueInterestPurchaseAgreementMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ArrangementsAndNonarrangementTransactionsMember_56fa096c-1eca-4d52-8086-5e0743a4682c" xlink:to="loc_espr_RevenueInterestPurchaseAgreementMember_612bf009-6d04-4c99-935c-adac39a8712a" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_RIPAAmendmentToTheSecurityAgreementAndWaiverMember_12aefa32-4af1-41b7-a6a2-fbf2c4367aa0" xlink:href="espr-20250630.xsd#espr_RIPAAmendmentToTheSecurityAgreementAndWaiverMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ArrangementsAndNonarrangementTransactionsMember_56fa096c-1eca-4d52-8086-5e0743a4682c" xlink:to="loc_espr_RIPAAmendmentToTheSecurityAgreementAndWaiverMember_12aefa32-4af1-41b7-a6a2-fbf2c4367aa0" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_CounterpartyNameAxis_68acbe4a-cc8c-4982-899a-d3e8b982c9d2" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_CounterpartyNameAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_DebtSecuritiesAvailableForSaleTable_600cd144-18c4-4567-90c8-57e7ffc32352" xlink:to="loc_srt_CounterpartyNameAxis_68acbe4a-cc8c-4982-899a-d3e8b982c9d2" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RepurchaseAgreementCounterpartyNameDomain_68acbe4a-cc8c-4982-899a-d3e8b982c9d2_default" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_RepurchaseAgreementCounterpartyNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_CounterpartyNameAxis_68acbe4a-cc8c-4982-899a-d3e8b982c9d2" xlink:to="loc_srt_RepurchaseAgreementCounterpartyNameDomain_68acbe4a-cc8c-4982-899a-d3e8b982c9d2_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RepurchaseAgreementCounterpartyNameDomain_7bf034a3-d3b2-4e67-86ef-cf0617afc009" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_RepurchaseAgreementCounterpartyNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_CounterpartyNameAxis_68acbe4a-cc8c-4982-899a-d3e8b982c9d2" xlink:to="loc_srt_RepurchaseAgreementCounterpartyNameDomain_7bf034a3-d3b2-4e67-86ef-cf0617afc009" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_EigerIiiSaLlcMember_641caad1-483f-40ef-a538-a22e4db4d29d" xlink:href="espr-20250630.xsd#espr_EigerIiiSaLlcMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_RepurchaseAgreementCounterpartyNameDomain_7bf034a3-d3b2-4e67-86ef-cf0617afc009" xlink:to="loc_espr_EigerIiiSaLlcMember_641caad1-483f-40ef-a538-a22e4db4d29d" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_GrossProceedsFromRevenueInterestPurchaseAgreement_c08acda4-5308-4d44-b329-97911a755df7" xlink:href="espr-20250630.xsd#espr_GrossProceedsFromRevenueInterestPurchaseAgreement"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ScheduleOfAvailableForSaleSecuritiesLineItems_614d3f34-5dd3-4ac8-8e24-d65b886e3ad9" xlink:to="loc_espr_GrossProceedsFromRevenueInterestPurchaseAgreement_c08acda4-5308-4d44-b329-97911a755df7" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_AmountOfSubsequentInstallmentSubjectToRevenueInterestPurchaseAgreementTermsAndConditions_b4ddcc4d-8257-44cc-ba79-0814f568a88f" xlink:href="espr-20250630.xsd#espr_AmountOfSubsequentInstallmentSubjectToRevenueInterestPurchaseAgreementTermsAndConditions"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ScheduleOfAvailableForSaleSecuritiesLineItems_614d3f34-5dd3-4ac8-8e24-d65b886e3ad9" xlink:to="loc_espr_AmountOfSubsequentInstallmentSubjectToRevenueInterestPurchaseAgreementTermsAndConditions_b4ddcc4d-8257-44cc-ba79-0814f568a88f" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_AmountOfSubsequentInstallmentSubjectToRegulatoryApproval_6e1e7a20-ae9c-4475-91f5-ce4f77ac4e68" xlink:href="espr-20250630.xsd#espr_AmountOfSubsequentInstallmentSubjectToRegulatoryApproval"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ScheduleOfAvailableForSaleSecuritiesLineItems_614d3f34-5dd3-4ac8-8e24-d65b886e3ad9" xlink:to="loc_espr_AmountOfSubsequentInstallmentSubjectToRegulatoryApproval_6e1e7a20-ae9c-4475-91f5-ce4f77ac4e68" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_AmountOfSubsequentInstallmentSubjectToAchievementOfSalesThreshold_9f51ea81-5f73-4e90-8d5b-bb0e24188b24" xlink:href="espr-20250630.xsd#espr_AmountOfSubsequentInstallmentSubjectToAchievementOfSalesThreshold"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ScheduleOfAvailableForSaleSecuritiesLineItems_614d3f34-5dd3-4ac8-8e24-d65b886e3ad9" xlink:to="loc_espr_AmountOfSubsequentInstallmentSubjectToAchievementOfSalesThreshold_9f51ea81-5f73-4e90-8d5b-bb0e24188b24" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_MilestoneAmountForWorldwideSalesToReceiveThirdPayment_56811344-75ed-4d91-a08d-f996b3a6a217" xlink:href="espr-20250630.xsd#espr_MilestoneAmountForWorldwideSalesToReceiveThirdPayment"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ScheduleOfAvailableForSaleSecuritiesLineItems_614d3f34-5dd3-4ac8-8e24-d65b886e3ad9" xlink:to="loc_espr_MilestoneAmountForWorldwideSalesToReceiveThirdPayment_56811344-75ed-4d91-a08d-f996b3a6a217" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_ProceedsFromRevenueInterestPurchaseAgreement_df55866f-d027-4739-a13b-f4b6c03d15b8" xlink:href="espr-20250630.xsd#espr_ProceedsFromRevenueInterestPurchaseAgreement"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ScheduleOfAvailableForSaleSecuritiesLineItems_614d3f34-5dd3-4ac8-8e24-d65b886e3ad9" xlink:to="loc_espr_ProceedsFromRevenueInterestPurchaseAgreement_df55866f-d027-4739-a13b-f4b6c03d15b8" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_RevenueInterestRateTierTwo_27c7b76e-7098-4483-83df-3f882f4a8204" xlink:href="espr-20250630.xsd#espr_RevenueInterestRateTierTwo"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ScheduleOfAvailableForSaleSecuritiesLineItems_614d3f34-5dd3-4ac8-8e24-d65b886e3ad9" xlink:to="loc_espr_RevenueInterestRateTierTwo_27c7b76e-7098-4483-83df-3f882f4a8204" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_RevenueInterestRateInitialRate_280ad8db-6055-42ff-9be0-ef977fcc16d8" xlink:href="espr-20250630.xsd#espr_RevenueInterestRateInitialRate"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ScheduleOfAvailableForSaleSecuritiesLineItems_614d3f34-5dd3-4ac8-8e24-d65b886e3ad9" xlink:to="loc_espr_RevenueInterestRateInitialRate_280ad8db-6055-42ff-9be0-ef977fcc16d8" xlink:type="arc" order="7"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_PercentageOfInvestedCapitalReceivedByDecember312024ToQualifyForSecondReducedRevenueInterestRate_a2cadf38-4dc2-4433-baa3-a1a42cf99ea8" xlink:href="espr-20250630.xsd#espr_PercentageOfInvestedCapitalReceivedByDecember312024ToQualifyForSecondReducedRevenueInterestRate"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ScheduleOfAvailableForSaleSecuritiesLineItems_614d3f34-5dd3-4ac8-8e24-d65b886e3ad9" xlink:to="loc_espr_PercentageOfInvestedCapitalReceivedByDecember312024ToQualifyForSecondReducedRevenueInterestRate_a2cadf38-4dc2-4433-baa3-a1a42cf99ea8" xlink:type="arc" order="8"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_RevenueInterestRateTierThree_385f0fb3-c172-49ad-af0e-c962578cb865" xlink:href="espr-20250630.xsd#espr_RevenueInterestRateTierThree"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ScheduleOfAvailableForSaleSecuritiesLineItems_614d3f34-5dd3-4ac8-8e24-d65b886e3ad9" xlink:to="loc_espr_RevenueInterestRateTierThree_385f0fb3-c172-49ad-af0e-c962578cb865" xlink:type="arc" order="9"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_PercentageOfIncreaseInRoyaltyRateUponDrawdownOfThirdPayment_c75bd524-a1a4-42b9-935a-ecd6c302fb5c" xlink:href="espr-20250630.xsd#espr_PercentageOfIncreaseInRoyaltyRateUponDrawdownOfThirdPayment"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ScheduleOfAvailableForSaleSecuritiesLineItems_614d3f34-5dd3-4ac8-8e24-d65b886e3ad9" xlink:to="loc_espr_PercentageOfIncreaseInRoyaltyRateUponDrawdownOfThirdPayment_c75bd524-a1a4-42b9-935a-ecd6c302fb5c" xlink:type="arc" order="10"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_MinimumAmountOfAnnualNetSalesToQualifyForReducedRevenueInterestRate_2fd95cb8-2628-4966-98fa-b86bb2256620" xlink:href="espr-20250630.xsd#espr_MinimumAmountOfAnnualNetSalesToQualifyForReducedRevenueInterestRate"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ScheduleOfAvailableForSaleSecuritiesLineItems_614d3f34-5dd3-4ac8-8e24-d65b886e3ad9" xlink:to="loc_espr_MinimumAmountOfAnnualNetSalesToQualifyForReducedRevenueInterestRate_2fd95cb8-2628-4966-98fa-b86bb2256620" xlink:type="arc" order="11"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_PercentageOfRevenueInterestsPaymentOnWhichAgreementTerminates_b9a89554-cc4c-433e-83bd-efe37420cfb1" xlink:href="espr-20250630.xsd#espr_PercentageOfRevenueInterestsPaymentOnWhichAgreementTerminates"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ScheduleOfAvailableForSaleSecuritiesLineItems_614d3f34-5dd3-4ac8-8e24-d65b886e3ad9" xlink:to="loc_espr_PercentageOfRevenueInterestsPaymentOnWhichAgreementTerminates_b9a89554-cc4c-433e-83bd-efe37420cfb1" xlink:type="arc" order="12"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_TrailingNumberOfMonthsSalesMustBeAtOrAboveMilestoneAmount_acd8c568-7227-43da-820a-9992b096ec93" xlink:href="espr-20250630.xsd#espr_TrailingNumberOfMonthsSalesMustBeAtOrAboveMilestoneAmount"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ScheduleOfAvailableForSaleSecuritiesLineItems_614d3f34-5dd3-4ac8-8e24-d65b886e3ad9" xlink:to="loc_espr_TrailingNumberOfMonthsSalesMustBeAtOrAboveMilestoneAmount_acd8c568-7227-43da-820a-9992b096ec93" xlink:type="arc" order="13"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_SpecifiedNetRevenueThresholdTriggeringDepositInBlockedAccount_5dba97eb-17a5-493e-a90e-e61e502c553a" xlink:href="espr-20250630.xsd#espr_SpecifiedNetRevenueThresholdTriggeringDepositInBlockedAccount"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ScheduleOfAvailableForSaleSecuritiesLineItems_614d3f34-5dd3-4ac8-8e24-d65b886e3ad9" xlink:to="loc_espr_SpecifiedNetRevenueThresholdTriggeringDepositInBlockedAccount_5dba97eb-17a5-493e-a90e-e61e502c553a" xlink:type="arc" order="14"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RestrictedCash_58702bd7-b631-4fba-9766-40c6a7e981ec" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_RestrictedCash"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ScheduleOfAvailableForSaleSecuritiesLineItems_614d3f34-5dd3-4ac8-8e24-d65b886e3ad9" xlink:to="loc_us-gaap_RestrictedCash_58702bd7-b631-4fba-9766-40c6a7e981ec" xlink:type="arc" order="15"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_OneTimePartialCall_1af9c4de-10a7-4f11-931b-0e2c59965804" xlink:href="espr-20250630.xsd#espr_OneTimePartialCall"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ScheduleOfAvailableForSaleSecuritiesLineItems_614d3f34-5dd3-4ac8-8e24-d65b886e3ad9" xlink:to="loc_espr_OneTimePartialCall_1af9c4de-10a7-4f11-931b-0e2c59965804" xlink:type="arc" order="16"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_RevenueInterestsPaymentOnWhichAgreementTerminates_b04d0c1e-1f31-4dcd-9636-60ac260da9a1" xlink:href="espr-20250630.xsd#espr_RevenueInterestsPaymentOnWhichAgreementTerminates"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ScheduleOfAvailableForSaleSecuritiesLineItems_614d3f34-5dd3-4ac8-8e24-d65b886e3ad9" xlink:to="loc_espr_RevenueInterestsPaymentOnWhichAgreementTerminates_b04d0c1e-1f31-4dcd-9636-60ac260da9a1" xlink:type="arc" order="17"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_PaymentsForRepurchaseOfRevenueInterests_01200691-f585-412b-a597-f6e17dd9a337" xlink:href="espr-20250630.xsd#espr_PaymentsForRepurchaseOfRevenueInterests"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ScheduleOfAvailableForSaleSecuritiesLineItems_614d3f34-5dd3-4ac8-8e24-d65b886e3ad9" xlink:to="loc_espr_PaymentsForRepurchaseOfRevenueInterests_01200691-f585-412b-a597-f6e17dd9a337" xlink:type="arc" order="18"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_GainsLossesOnExtinguishmentOfDebt_6a712dae-998f-44c0-ba42-3ba26008a30b" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_GainsLossesOnExtinguishmentOfDebt"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ScheduleOfAvailableForSaleSecuritiesLineItems_614d3f34-5dd3-4ac8-8e24-d65b886e3ad9" xlink:to="loc_us-gaap_GainsLossesOnExtinguishmentOfDebt_6a712dae-998f-44c0-ba42-3ba26008a30b" xlink:type="arc" order="19"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_InterestExpenseNonoperating_8d2de88a-3add-4595-a9d2-f629bb93d677" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_InterestExpenseNonoperating"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ScheduleOfAvailableForSaleSecuritiesLineItems_614d3f34-5dd3-4ac8-8e24-d65b886e3ad9" xlink:to="loc_us-gaap_InterestExpenseNonoperating_8d2de88a-3add-4595-a9d2-f629bb93d677" xlink:type="arc" order="20"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.esperion.com/role/SaleofFutureRoyaltiesNarrativeDetails" xlink:type="simple" xlink:href="espr-20250630.xsd#SaleofFutureRoyaltiesNarrativeDetails"/>
  <link:definitionLink xlink:role="http://www.esperion.com/role/SaleofFutureRoyaltiesNarrativeDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentLineItems_621f963d-44b6-4e00-80ef-ab89ec107fc5" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_DebtInstrumentLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentTable_d4c585ce-5f5d-4faf-b5dd-87b7b5427106" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_DebtInstrumentTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_DebtInstrumentLineItems_621f963d-44b6-4e00-80ef-ab89ec107fc5" xlink:to="loc_us-gaap_DebtInstrumentTable_d4c585ce-5f5d-4faf-b5dd-87b7b5427106" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentAxis_2214031b-8edd-40ed-96ec-7ed2ef962af2" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_DebtInstrumentAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_DebtInstrumentTable_d4c585ce-5f5d-4faf-b5dd-87b7b5427106" xlink:to="loc_us-gaap_DebtInstrumentAxis_2214031b-8edd-40ed-96ec-7ed2ef962af2" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentNameDomain_2214031b-8edd-40ed-96ec-7ed2ef962af2_default" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_DebtInstrumentNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_DebtInstrumentAxis_2214031b-8edd-40ed-96ec-7ed2ef962af2" xlink:to="loc_us-gaap_DebtInstrumentNameDomain_2214031b-8edd-40ed-96ec-7ed2ef962af2_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentNameDomain_34fa04e3-e192-4965-8e2e-36dd80f53ba9" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_DebtInstrumentNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_DebtInstrumentAxis_2214031b-8edd-40ed-96ec-7ed2ef962af2" xlink:to="loc_us-gaap_DebtInstrumentNameDomain_34fa04e3-e192-4965-8e2e-36dd80f53ba9" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_SaleOfFutureRoyaltiesMember_86554703-794b-4be0-bef2-4dd007ee2cb4" xlink:href="espr-20250630.xsd#espr_SaleOfFutureRoyaltiesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentNameDomain_34fa04e3-e192-4965-8e2e-36dd80f53ba9" xlink:to="loc_espr_SaleOfFutureRoyaltiesMember_86554703-794b-4be0-bef2-4dd007ee2cb4" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_RoyaltySaleConsiderationReceived_c6e55a8a-7ddb-499e-95b0-8fab8ea69528" xlink:href="espr-20250630.xsd#espr_RoyaltySaleConsiderationReceived"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_621f963d-44b6-4e00-80ef-ab89ec107fc5" xlink:to="loc_espr_RoyaltySaleConsiderationReceived_c6e55a8a-7ddb-499e-95b0-8fab8ea69528" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PaymentsOfDebtIssuanceCosts_eb3c296f-c422-46c9-b661-775d2da4a3f3" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_PaymentsOfDebtIssuanceCosts"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_621f963d-44b6-4e00-80ef-ab89ec107fc5" xlink:to="loc_us-gaap_PaymentsOfDebtIssuanceCosts_eb3c296f-c422-46c9-b661-775d2da4a3f3" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_SaleOfFutureRoyaltiesPercentageRoyaltyInterestsAcquired_37258435-2807-4088-bbb4-3abbd803d21a" xlink:href="espr-20250630.xsd#espr_SaleOfFutureRoyaltiesPercentageRoyaltyInterestsAcquired"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_621f963d-44b6-4e00-80ef-ab89ec107fc5" xlink:to="loc_espr_SaleOfFutureRoyaltiesPercentageRoyaltyInterestsAcquired_37258435-2807-4088-bbb4-3abbd803d21a" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_SaleOfFutureRoyaltiesThresholdPurchasePriceMultiplier_350c55b6-80a1-4ebc-a6d5-c83cd91f3c90" xlink:href="espr-20250630.xsd#espr_SaleOfFutureRoyaltiesThresholdPurchasePriceMultiplier"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_621f963d-44b6-4e00-80ef-ab89ec107fc5" xlink:to="loc_espr_SaleOfFutureRoyaltiesThresholdPurchasePriceMultiplier_350c55b6-80a1-4ebc-a6d5-c83cd91f3c90" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_SaleOfFutureRoyaltiesThresholdAmountPurchaserWillReceivePriorToInterestsRevertingBackToCompany_e430d8d4-fdde-4f57-9ea1-d3d4f9f1a347" xlink:href="espr-20250630.xsd#espr_SaleOfFutureRoyaltiesThresholdAmountPurchaserWillReceivePriorToInterestsRevertingBackToCompany"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_621f963d-44b6-4e00-80ef-ab89ec107fc5" xlink:to="loc_espr_SaleOfFutureRoyaltiesThresholdAmountPurchaserWillReceivePriorToInterestsRevertingBackToCompany_e430d8d4-fdde-4f57-9ea1-d3d4f9f1a347" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_SaleOfFutureRoyaltiesPercentageRoyaltyInterestsRevertedToCompanyFollowingReceiptOfThresholdPurchasePriceMultiple_6d32c159-e122-4e8b-8d21-a331df045da3" xlink:href="espr-20250630.xsd#espr_SaleOfFutureRoyaltiesPercentageRoyaltyInterestsRevertedToCompanyFollowingReceiptOfThresholdPurchasePriceMultiple"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_621f963d-44b6-4e00-80ef-ab89ec107fc5" xlink:to="loc_espr_SaleOfFutureRoyaltiesPercentageRoyaltyInterestsRevertedToCompanyFollowingReceiptOfThresholdPurchasePriceMultiple_6d32c159-e122-4e8b-8d21-a331df045da3" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_RoyaltySaleLiability_a26c0af4-d9e2-4b01-9a47-cefa44bcc44b" xlink:href="espr-20250630.xsd#espr_RoyaltySaleLiability"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_621f963d-44b6-4e00-80ef-ab89ec107fc5" xlink:to="loc_espr_RoyaltySaleLiability_a26c0af4-d9e2-4b01-9a47-cefa44bcc44b" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_RoyaltySaleLiabilityCapitalizedIssuanceCosts_6cb9006a-4908-4b9f-975e-335c6b147157" xlink:href="espr-20250630.xsd#espr_RoyaltySaleLiabilityCapitalizedIssuanceCosts"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_621f963d-44b6-4e00-80ef-ab89ec107fc5" xlink:to="loc_espr_RoyaltySaleLiabilityCapitalizedIssuanceCosts_6cb9006a-4908-4b9f-975e-335c6b147157" xlink:type="arc" order="7"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_RoyaltySaleLiabilityCapitalizedIssuanceCostsAmortizedExpenseYearOne_4627577c-e076-4cec-aac1-157d6620767e" xlink:href="espr-20250630.xsd#espr_RoyaltySaleLiabilityCapitalizedIssuanceCostsAmortizedExpenseYearOne"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_621f963d-44b6-4e00-80ef-ab89ec107fc5" xlink:to="loc_espr_RoyaltySaleLiabilityCapitalizedIssuanceCostsAmortizedExpenseYearOne_4627577c-e076-4cec-aac1-157d6620767e" xlink:type="arc" order="8"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_RoyaltySaleLiabilityCapitalizedIssuanceCostsAmortizedExpenseYearTwoAndThereafter_2c9134a0-9eac-47f9-a7f8-d53bee074083" xlink:href="espr-20250630.xsd#espr_RoyaltySaleLiabilityCapitalizedIssuanceCostsAmortizedExpenseYearTwoAndThereafter"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_621f963d-44b6-4e00-80ef-ab89ec107fc5" xlink:to="loc_espr_RoyaltySaleLiabilityCapitalizedIssuanceCostsAmortizedExpenseYearTwoAndThereafter_2c9134a0-9eac-47f9-a7f8-d53bee074083" xlink:type="arc" order="9"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_RoyaltySaleLiabilityCurrent_90ee41b3-34d9-4b64-a4bd-73a1642a60d4" xlink:href="espr-20250630.xsd#espr_RoyaltySaleLiabilityCurrent"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_621f963d-44b6-4e00-80ef-ab89ec107fc5" xlink:to="loc_espr_RoyaltySaleLiabilityCurrent_90ee41b3-34d9-4b64-a4bd-73a1642a60d4" xlink:type="arc" order="10"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_SaleOfFutureRoyaltiesEffectiveAnnualImputedInterestRate_40329297-e77b-4957-a53d-9b745815c451" xlink:href="espr-20250630.xsd#espr_SaleOfFutureRoyaltiesEffectiveAnnualImputedInterestRate"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_621f963d-44b6-4e00-80ef-ab89ec107fc5" xlink:to="loc_espr_SaleOfFutureRoyaltiesEffectiveAnnualImputedInterestRate_40329297-e77b-4957-a53d-9b745815c451" xlink:type="arc" order="11"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AmortizationOfFinancingCosts_ec1267df-8514-4e7a-8b36-f93d44d1c1ac" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_AmortizationOfFinancingCosts"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_621f963d-44b6-4e00-80ef-ab89ec107fc5" xlink:to="loc_us-gaap_AmortizationOfFinancingCosts_ec1267df-8514-4e7a-8b36-f93d44d1c1ac" xlink:type="arc" order="12"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.esperion.com/role/SaleofFutureRoyaltiesScheduleofActivityWithinRoyaltySaleLiabilityDetails" xlink:type="simple" xlink:href="espr-20250630.xsd#SaleofFutureRoyaltiesScheduleofActivityWithinRoyaltySaleLiabilityDetails"/>
  <link:definitionLink xlink:role="http://www.esperion.com/role/SaleofFutureRoyaltiesScheduleofActivityWithinRoyaltySaleLiabilityDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentLineItems_db57c668-f6fc-4569-b706-109f041c4f10" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_DebtInstrumentLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentTable_63cbf312-98c8-4109-9474-7ad9f448d275" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_DebtInstrumentTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_DebtInstrumentLineItems_db57c668-f6fc-4569-b706-109f041c4f10" xlink:to="loc_us-gaap_DebtInstrumentTable_63cbf312-98c8-4109-9474-7ad9f448d275" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentAxis_ed17bd8f-759a-41df-85a8-256eb87617fe" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_DebtInstrumentAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_DebtInstrumentTable_63cbf312-98c8-4109-9474-7ad9f448d275" xlink:to="loc_us-gaap_DebtInstrumentAxis_ed17bd8f-759a-41df-85a8-256eb87617fe" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentNameDomain_ed17bd8f-759a-41df-85a8-256eb87617fe_default" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_DebtInstrumentNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_DebtInstrumentAxis_ed17bd8f-759a-41df-85a8-256eb87617fe" xlink:to="loc_us-gaap_DebtInstrumentNameDomain_ed17bd8f-759a-41df-85a8-256eb87617fe_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentNameDomain_3214c6b7-88f6-446e-ab24-494c684bb005" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_DebtInstrumentNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_DebtInstrumentAxis_ed17bd8f-759a-41df-85a8-256eb87617fe" xlink:to="loc_us-gaap_DebtInstrumentNameDomain_3214c6b7-88f6-446e-ab24-494c684bb005" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_SaleOfFutureRoyaltiesMember_d8926765-c7ca-4e8f-95d2-8d9be19f55d8" xlink:href="espr-20250630.xsd#espr_SaleOfFutureRoyaltiesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentNameDomain_3214c6b7-88f6-446e-ab24-494c684bb005" xlink:to="loc_espr_SaleOfFutureRoyaltiesMember_d8926765-c7ca-4e8f-95d2-8d9be19f55d8" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_SaleOfFutureRoyaltiesRollForward_9d389c59-b79f-4589-bbb6-0a92c103326e" xlink:href="espr-20250630.xsd#espr_SaleOfFutureRoyaltiesRollForward"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_db57c668-f6fc-4569-b706-109f041c4f10" xlink:to="loc_espr_SaleOfFutureRoyaltiesRollForward_9d389c59-b79f-4589-bbb6-0a92c103326e" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_RoyaltySaleLiability_c326b2d7-ae90-4431-a920-f3f2e757e361" xlink:href="espr-20250630.xsd#espr_RoyaltySaleLiability"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_espr_SaleOfFutureRoyaltiesRollForward_9d389c59-b79f-4589-bbb6-0a92c103326e" xlink:to="loc_espr_RoyaltySaleLiability_c326b2d7-ae90-4431-a920-f3f2e757e361" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_RoyaltySaleLiabilityDecreaseForRoyaltiesRecognized_8deaa44d-416b-4ba3-9ca4-6cd5f56a2df1" xlink:href="espr-20250630.xsd#espr_RoyaltySaleLiabilityDecreaseForRoyaltiesRecognized"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_espr_SaleOfFutureRoyaltiesRollForward_9d389c59-b79f-4589-bbb6-0a92c103326e" xlink:to="loc_espr_RoyaltySaleLiabilityDecreaseForRoyaltiesRecognized_8deaa44d-416b-4ba3-9ca4-6cd5f56a2df1" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_InterestExpenseNonoperating_e66104c5-ebe3-4588-a6e4-75630beaf4c1" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_InterestExpenseNonoperating"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_espr_SaleOfFutureRoyaltiesRollForward_9d389c59-b79f-4589-bbb6-0a92c103326e" xlink:to="loc_us-gaap_InterestExpenseNonoperating_e66104c5-ebe3-4588-a6e4-75630beaf4c1" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_RoyaltySaleLiability_b09738cc-d032-478e-82cd-62ada86a2d85" xlink:href="espr-20250630.xsd#espr_RoyaltySaleLiability"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.esperion.com/role/DebtDetails" xlink:type="simple" xlink:href="espr-20250630.xsd#DebtDetails"/>
  <link:definitionLink xlink:role="http://www.esperion.com/role/DebtDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentLineItems_d627fcbc-a124-4453-b5ee-02e686640eef" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_DebtInstrumentLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentTable_bbd86bb6-a676-469e-aa76-f4cd913ebbd4" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_DebtInstrumentTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_DebtInstrumentLineItems_d627fcbc-a124-4453-b5ee-02e686640eef" xlink:to="loc_us-gaap_DebtInstrumentTable_bbd86bb6-a676-469e-aa76-f4cd913ebbd4" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentAxis_06e2a390-6173-427e-9f04-b59daac3309c" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_DebtInstrumentAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_DebtInstrumentTable_bbd86bb6-a676-469e-aa76-f4cd913ebbd4" xlink:to="loc_us-gaap_DebtInstrumentAxis_06e2a390-6173-427e-9f04-b59daac3309c" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentNameDomain_06e2a390-6173-427e-9f04-b59daac3309c_default" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_DebtInstrumentNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_DebtInstrumentAxis_06e2a390-6173-427e-9f04-b59daac3309c" xlink:to="loc_us-gaap_DebtInstrumentNameDomain_06e2a390-6173-427e-9f04-b59daac3309c_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentNameDomain_987cf76b-d147-451f-9606-668dbdf5b646" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_DebtInstrumentNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_DebtInstrumentAxis_06e2a390-6173-427e-9f04-b59daac3309c" xlink:to="loc_us-gaap_DebtInstrumentNameDomain_987cf76b-d147-451f-9606-668dbdf5b646" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_CreditAgreementMember_2877b0eb-fcf8-48cc-aa3f-ce4a96326f08" xlink:href="espr-20250630.xsd#espr_CreditAgreementMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentNameDomain_987cf76b-d147-451f-9606-668dbdf5b646" xlink:to="loc_espr_CreditAgreementMember_2877b0eb-fcf8-48cc-aa3f-ce4a96326f08" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_ConvertibleSeniorNotesDue2025Member_92f16439-d21d-410a-8f26-cfb72fd0597e" xlink:href="espr-20250630.xsd#espr_ConvertibleSeniorNotesDue2025Member"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentNameDomain_987cf76b-d147-451f-9606-668dbdf5b646" xlink:to="loc_espr_ConvertibleSeniorNotesDue2025Member_92f16439-d21d-410a-8f26-cfb72fd0597e" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_ConvertibleSeniorNotesDue2030Member_87539511-fd13-4e9d-b107-1c4d4c736287" xlink:href="espr-20250630.xsd#espr_ConvertibleSeniorNotesDue2030Member"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentNameDomain_987cf76b-d147-451f-9606-668dbdf5b646" xlink:to="loc_espr_ConvertibleSeniorNotesDue2030Member_87539511-fd13-4e9d-b107-1c4d4c736287" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_ConvertibleSeniorNotesDue2030ExchangeTransactionsMember_7dfcca2d-a122-475e-88a7-74ab92a05561" xlink:href="espr-20250630.xsd#espr_ConvertibleSeniorNotesDue2030ExchangeTransactionsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_espr_ConvertibleSeniorNotesDue2030Member_87539511-fd13-4e9d-b107-1c4d4c736287" xlink:to="loc_espr_ConvertibleSeniorNotesDue2030ExchangeTransactionsMember_7dfcca2d-a122-475e-88a7-74ab92a05561" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_ConvertibleSeniorNotesDue2030SubscriptionTransactionsMember_17f97b42-7bab-4fc8-ba60-f28e74162d54" xlink:href="espr-20250630.xsd#espr_ConvertibleSeniorNotesDue2030SubscriptionTransactionsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_espr_ConvertibleSeniorNotesDue2030Member_87539511-fd13-4e9d-b107-1c4d4c736287" xlink:to="loc_espr_ConvertibleSeniorNotesDue2030SubscriptionTransactionsMember_17f97b42-7bab-4fc8-ba60-f28e74162d54" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LongtermDebtTypeAxis_1f537d9c-da9e-4c53-bcdc-3070f545151d" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_LongtermDebtTypeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_DebtInstrumentTable_bbd86bb6-a676-469e-aa76-f4cd913ebbd4" xlink:to="loc_us-gaap_LongtermDebtTypeAxis_1f537d9c-da9e-4c53-bcdc-3070f545151d" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LongtermDebtTypeDomain_1f537d9c-da9e-4c53-bcdc-3070f545151d_default" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_LongtermDebtTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_LongtermDebtTypeAxis_1f537d9c-da9e-4c53-bcdc-3070f545151d" xlink:to="loc_us-gaap_LongtermDebtTypeDomain_1f537d9c-da9e-4c53-bcdc-3070f545151d_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LongtermDebtTypeDomain_fc6cc1d4-7eb2-477f-a4d9-689fb2484d10" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_LongtermDebtTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_LongtermDebtTypeAxis_1f537d9c-da9e-4c53-bcdc-3070f545151d" xlink:to="loc_us-gaap_LongtermDebtTypeDomain_fc6cc1d4-7eb2-477f-a4d9-689fb2484d10" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LineOfCreditMember_7f0152c5-27e9-43d6-ae2b-f5bdf0827b1e" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_LineOfCreditMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LongtermDebtTypeDomain_fc6cc1d4-7eb2-477f-a4d9-689fb2484d10" xlink:to="loc_us-gaap_LineOfCreditMember_7f0152c5-27e9-43d6-ae2b-f5bdf0827b1e" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ConvertibleDebtMember_01bea2ca-ee8c-4d05-a108-3e11d8619c54" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ConvertibleDebtMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LongtermDebtTypeDomain_fc6cc1d4-7eb2-477f-a4d9-689fb2484d10" xlink:to="loc_us-gaap_ConvertibleDebtMember_01bea2ca-ee8c-4d05-a108-3e11d8619c54" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentRedemptionPeriodAxis_58bfbb21-8568-4835-b07b-768be65aaadf" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_DebtInstrumentRedemptionPeriodAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_DebtInstrumentTable_bbd86bb6-a676-469e-aa76-f4cd913ebbd4" xlink:to="loc_us-gaap_DebtInstrumentRedemptionPeriodAxis_58bfbb21-8568-4835-b07b-768be65aaadf" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentRedemptionPeriodDomain_58bfbb21-8568-4835-b07b-768be65aaadf_default" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_DebtInstrumentRedemptionPeriodDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_DebtInstrumentRedemptionPeriodAxis_58bfbb21-8568-4835-b07b-768be65aaadf" xlink:to="loc_us-gaap_DebtInstrumentRedemptionPeriodDomain_58bfbb21-8568-4835-b07b-768be65aaadf_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentRedemptionPeriodDomain_1e554696-ad17-40d6-9289-91c388bd7c18" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_DebtInstrumentRedemptionPeriodDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_DebtInstrumentRedemptionPeriodAxis_58bfbb21-8568-4835-b07b-768be65aaadf" xlink:to="loc_us-gaap_DebtInstrumentRedemptionPeriodDomain_1e554696-ad17-40d6-9289-91c388bd7c18" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentRedemptionPeriodOneMember_dab3f179-fca1-43d3-9440-b2af96fdaaab" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_DebtInstrumentRedemptionPeriodOneMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentRedemptionPeriodDomain_1e554696-ad17-40d6-9289-91c388bd7c18" xlink:to="loc_us-gaap_DebtInstrumentRedemptionPeriodOneMember_dab3f179-fca1-43d3-9440-b2af96fdaaab" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentRedemptionPeriodTwoMember_e50a3b28-49d9-41d9-9f4e-cd0a6fdcce97" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_DebtInstrumentRedemptionPeriodTwoMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentRedemptionPeriodDomain_1e554696-ad17-40d6-9289-91c388bd7c18" xlink:to="loc_us-gaap_DebtInstrumentRedemptionPeriodTwoMember_e50a3b28-49d9-41d9-9f4e-cd0a6fdcce97" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ClassOfWarrantOrRightAxis_d1df5073-9a2b-40c7-8121-299ee98120d2" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ClassOfWarrantOrRightAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_DebtInstrumentTable_bbd86bb6-a676-469e-aa76-f4cd913ebbd4" xlink:to="loc_us-gaap_ClassOfWarrantOrRightAxis_d1df5073-9a2b-40c7-8121-299ee98120d2" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ClassOfWarrantOrRightDomain_d1df5073-9a2b-40c7-8121-299ee98120d2_default" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ClassOfWarrantOrRightDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_ClassOfWarrantOrRightAxis_d1df5073-9a2b-40c7-8121-299ee98120d2" xlink:to="loc_us-gaap_ClassOfWarrantOrRightDomain_d1df5073-9a2b-40c7-8121-299ee98120d2_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ClassOfWarrantOrRightDomain_d4fab98a-f7a7-45cf-ba15-3bc7d5151c27" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ClassOfWarrantOrRightDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_ClassOfWarrantOrRightAxis_d1df5073-9a2b-40c7-8121-299ee98120d2" xlink:to="loc_us-gaap_ClassOfWarrantOrRightDomain_d4fab98a-f7a7-45cf-ba15-3bc7d5151c27" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_CappedCallMember_62fbf4a8-5f9e-445f-ae57-1b3616b35fbb" xlink:href="espr-20250630.xsd#espr_CappedCallMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfWarrantOrRightDomain_d4fab98a-f7a7-45cf-ba15-3bc7d5151c27" xlink:to="loc_espr_CappedCallMember_62fbf4a8-5f9e-445f-ae57-1b3616b35fbb" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StatementClassOfStockAxis_98336288-36be-4b3b-9546-59a56f7eb248" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_StatementClassOfStockAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_DebtInstrumentTable_bbd86bb6-a676-469e-aa76-f4cd913ebbd4" xlink:to="loc_us-gaap_StatementClassOfStockAxis_98336288-36be-4b3b-9546-59a56f7eb248" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ClassOfStockDomain_98336288-36be-4b3b-9546-59a56f7eb248_default" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ClassOfStockDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_StatementClassOfStockAxis_98336288-36be-4b3b-9546-59a56f7eb248" xlink:to="loc_us-gaap_ClassOfStockDomain_98336288-36be-4b3b-9546-59a56f7eb248_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ClassOfStockDomain_9f08e759-0196-40bd-92de-d1285aad6479" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ClassOfStockDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_StatementClassOfStockAxis_98336288-36be-4b3b-9546-59a56f7eb248" xlink:to="loc_us-gaap_ClassOfStockDomain_9f08e759-0196-40bd-92de-d1285aad6479" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CommonClassAMember_48a86e73-9c4d-422a-97a1-ebcbe6881e35" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_CommonClassAMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfStockDomain_9f08e759-0196-40bd-92de-d1285aad6479" xlink:to="loc_us-gaap_CommonClassAMember_48a86e73-9c4d-422a-97a1-ebcbe6881e35" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentFaceAmount_b538a9d4-2039-48a3-a930-3712aa2d6505" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_DebtInstrumentFaceAmount"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_d627fcbc-a124-4453-b5ee-02e686640eef" xlink:to="loc_us-gaap_DebtInstrumentFaceAmount_b538a9d4-2039-48a3-a930-3712aa2d6505" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RepaymentsOfDebt_5ae0987a-e1d5-459b-aaa2-97e44d133bb0" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_RepaymentsOfDebt"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_d627fcbc-a124-4453-b5ee-02e686640eef" xlink:to="loc_us-gaap_RepaymentsOfDebt_5ae0987a-e1d5-459b-aaa2-97e44d133bb0" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentInterestRateStatedPercentage_a565098e-cc59-4c2f-a671-cce3266979e9" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_DebtInstrumentInterestRateStatedPercentage"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_d627fcbc-a124-4453-b5ee-02e686640eef" xlink:to="loc_us-gaap_DebtInstrumentInterestRateStatedPercentage_a565098e-cc59-4c2f-a671-cce3266979e9" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_DebtInstrumentInterestRatePaidInCash_8ac9e3fe-6f10-435e-a385-356a831fcae2" xlink:href="espr-20250630.xsd#espr_DebtInstrumentInterestRatePaidInCash"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_d627fcbc-a124-4453-b5ee-02e686640eef" xlink:to="loc_espr_DebtInstrumentInterestRatePaidInCash_8ac9e3fe-6f10-435e-a385-356a831fcae2" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_DebtInstrumentInterestRatePaidInKind_d26bdf95-db36-4fc1-9566-e09b4262ca23" xlink:href="espr-20250630.xsd#espr_DebtInstrumentInterestRatePaidInKind"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_d627fcbc-a124-4453-b5ee-02e686640eef" xlink:to="loc_espr_DebtInstrumentInterestRatePaidInKind_d26bdf95-db36-4fc1-9566-e09b4262ca23" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_DebtInstrumentQuarterlyPrincipalRateAfterFourYears_cebaebbc-525c-4a38-8e9c-a32be67c4f6a" xlink:href="espr-20250630.xsd#espr_DebtInstrumentQuarterlyPrincipalRateAfterFourYears"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_d627fcbc-a124-4453-b5ee-02e686640eef" xlink:to="loc_espr_DebtInstrumentQuarterlyPrincipalRateAfterFourYears_cebaebbc-525c-4a38-8e9c-a32be67c4f6a" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LongTermDebtTerm_828b27d5-3c78-4e89-9ad5-b9a966f38cc4" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_LongTermDebtTerm"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_d627fcbc-a124-4453-b5ee-02e686640eef" xlink:to="loc_us-gaap_LongTermDebtTerm_828b27d5-3c78-4e89-9ad5-b9a966f38cc4" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_DebtInstrumentBasisSpreadOnMakeWholePremiumInNextTwoYears_d178337d-cbed-480c-9982-14f690a988ed" xlink:href="espr-20250630.xsd#espr_DebtInstrumentBasisSpreadOnMakeWholePremiumInNextTwoYears"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_d627fcbc-a124-4453-b5ee-02e686640eef" xlink:to="loc_espr_DebtInstrumentBasisSpreadOnMakeWholePremiumInNextTwoYears_d178337d-cbed-480c-9982-14f690a988ed" xlink:type="arc" order="7"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_DebtInstrumentPrepaymentPremiumYearThree_e267abed-ef04-43a8-92e0-445caf393540" xlink:href="espr-20250630.xsd#espr_DebtInstrumentPrepaymentPremiumYearThree"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_d627fcbc-a124-4453-b5ee-02e686640eef" xlink:to="loc_espr_DebtInstrumentPrepaymentPremiumYearThree_e267abed-ef04-43a8-92e0-445caf393540" xlink:type="arc" order="8"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_DebtInstrumentPrepaymentPremiumYearFour_7bdf9ec2-96d1-4230-9b2a-081df04a0e6e" xlink:href="espr-20250630.xsd#espr_DebtInstrumentPrepaymentPremiumYearFour"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_d627fcbc-a124-4453-b5ee-02e686640eef" xlink:to="loc_espr_DebtInstrumentPrepaymentPremiumYearFour_7bdf9ec2-96d1-4230-9b2a-081df04a0e6e" xlink:type="arc" order="9"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_DebtInstrumentCovenantMinimumLiquidity_e9a957f7-45b2-4dbf-8551-5ff6ea3abbb0" xlink:href="espr-20250630.xsd#espr_DebtInstrumentCovenantMinimumLiquidity"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_d627fcbc-a124-4453-b5ee-02e686640eef" xlink:to="loc_espr_DebtInstrumentCovenantMinimumLiquidity_e9a957f7-45b2-4dbf-8551-5ff6ea3abbb0" xlink:type="arc" order="10"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_DebtInstrumentOriginalDiscountPremiumPercentage_6c19b5de-63cc-4e90-83ac-9bbb7ac7b616" xlink:href="espr-20250630.xsd#espr_DebtInstrumentOriginalDiscountPremiumPercentage"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_d627fcbc-a124-4453-b5ee-02e686640eef" xlink:to="loc_espr_DebtInstrumentOriginalDiscountPremiumPercentage_6c19b5de-63cc-4e90-83ac-9bbb7ac7b616" xlink:type="arc" order="11"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentUnamortizedDiscount_09f1047a-10ab-41fa-838e-0e49737fb6c9" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_DebtInstrumentUnamortizedDiscount"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_d627fcbc-a124-4453-b5ee-02e686640eef" xlink:to="loc_us-gaap_DebtInstrumentUnamortizedDiscount_09f1047a-10ab-41fa-838e-0e49737fb6c9" xlink:type="arc" order="12"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DeferredFinanceCostsNet_90d05467-5f4a-4311-823d-f990931a3ae9" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_DeferredFinanceCostsNet"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_d627fcbc-a124-4453-b5ee-02e686640eef" xlink:to="loc_us-gaap_DeferredFinanceCostsNet_90d05467-5f4a-4311-823d-f990931a3ae9" xlink:type="arc" order="13"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PaidInKindInterest_f68d1983-44a0-47b2-b35d-7c7abfd23bd4" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_PaidInKindInterest"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_d627fcbc-a124-4453-b5ee-02e686640eef" xlink:to="loc_us-gaap_PaidInKindInterest_f68d1983-44a0-47b2-b35d-7c7abfd23bd4" xlink:type="arc" order="14"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OtherLongTermDebtNoncurrent_a9812ed6-b3c1-4e32-bce5-a097d21d128d" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_OtherLongTermDebtNoncurrent"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_d627fcbc-a124-4453-b5ee-02e686640eef" xlink:to="loc_us-gaap_OtherLongTermDebtNoncurrent_a9812ed6-b3c1-4e32-bce5-a097d21d128d" xlink:type="arc" order="15"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_InterestExpenseDebt_ae602d4a-18d1-42d4-b15f-0b945d8fd192" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_InterestExpenseDebt"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_d627fcbc-a124-4453-b5ee-02e686640eef" xlink:to="loc_us-gaap_InterestExpenseDebt_ae602d4a-18d1-42d4-b15f-0b945d8fd192" xlink:type="arc" order="16"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AmortizationOfFinancingCosts_c17911c3-8dcf-4bdb-8fd5-629def77faef" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_AmortizationOfFinancingCosts"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_d627fcbc-a124-4453-b5ee-02e686640eef" xlink:to="loc_us-gaap_AmortizationOfFinancingCosts_c17911c3-8dcf-4bdb-8fd5-629def77faef" xlink:type="arc" order="17"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AmortizationOfFinancingCostsAndDiscounts_9f7b80f8-79f8-4bf8-9fb2-bcc738eebff1" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_AmortizationOfFinancingCostsAndDiscounts"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_d627fcbc-a124-4453-b5ee-02e686640eef" xlink:to="loc_us-gaap_AmortizationOfFinancingCostsAndDiscounts_9f7b80f8-79f8-4bf8-9fb2-bcc738eebff1" xlink:type="arc" order="18"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ProceedsFromDebtNetOfIssuanceCosts_60ce3a5f-64bc-40eb-8b33-6afcaf46ebc0" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ProceedsFromDebtNetOfIssuanceCosts"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_d627fcbc-a124-4453-b5ee-02e686640eef" xlink:to="loc_us-gaap_ProceedsFromDebtNetOfIssuanceCosts_60ce3a5f-64bc-40eb-8b33-6afcaf46ebc0" xlink:type="arc" order="19"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PaymentsForDerivativeInstrumentFinancingActivities_d7699bc7-25ae-4050-87a3-ba64f83f3634" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_PaymentsForDerivativeInstrumentFinancingActivities"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_d627fcbc-a124-4453-b5ee-02e686640eef" xlink:to="loc_us-gaap_PaymentsForDerivativeInstrumentFinancingActivities_d7699bc7-25ae-4050-87a3-ba64f83f3634" xlink:type="arc" order="20"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PaymentsForRepurchaseOfCommonStock_394588c7-d0fb-47f6-b3d2-343ee6933786" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_PaymentsForRepurchaseOfCommonStock"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_d627fcbc-a124-4453-b5ee-02e686640eef" xlink:to="loc_us-gaap_PaymentsForRepurchaseOfCommonStock_394588c7-d0fb-47f6-b3d2-343ee6933786" xlink:type="arc" order="21"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CommonStockParOrStatedValuePerShare_89c186b9-6f2e-413c-8885-68ced9090038" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_CommonStockParOrStatedValuePerShare"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_d627fcbc-a124-4453-b5ee-02e686640eef" xlink:to="loc_us-gaap_CommonStockParOrStatedValuePerShare_89c186b9-6f2e-413c-8885-68ced9090038" xlink:type="arc" order="22"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentConvertibleConversionRatio1_464d2669-5b8f-48fb-a1d3-deb92191f507" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_DebtInstrumentConvertibleConversionRatio1"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_d627fcbc-a124-4453-b5ee-02e686640eef" xlink:to="loc_us-gaap_DebtInstrumentConvertibleConversionRatio1_464d2669-5b8f-48fb-a1d3-deb92191f507" xlink:type="arc" order="23"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentConvertibleConversionPrice1_aa252306-d2ba-45c7-9343-aa3a84dc1e76" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_DebtInstrumentConvertibleConversionPrice1"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_d627fcbc-a124-4453-b5ee-02e686640eef" xlink:to="loc_us-gaap_DebtInstrumentConvertibleConversionPrice1_aa252306-d2ba-45c7-9343-aa3a84dc1e76" xlink:type="arc" order="24"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentConvertibleThresholdPercentageOfStockPriceTrigger_e7b87752-c5ee-43da-a45b-a3cd65bb7391" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_DebtInstrumentConvertibleThresholdPercentageOfStockPriceTrigger"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_d627fcbc-a124-4453-b5ee-02e686640eef" xlink:to="loc_us-gaap_DebtInstrumentConvertibleThresholdPercentageOfStockPriceTrigger_e7b87752-c5ee-43da-a45b-a3cd65bb7391" xlink:type="arc" order="25"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentConvertibleThresholdTradingDays_3fb6182a-d6fb-4b03-abc2-1e0cecb31933" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_DebtInstrumentConvertibleThresholdTradingDays"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_d627fcbc-a124-4453-b5ee-02e686640eef" xlink:to="loc_us-gaap_DebtInstrumentConvertibleThresholdTradingDays_3fb6182a-d6fb-4b03-abc2-1e0cecb31933" xlink:type="arc" order="26"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentConvertibleThresholdConsecutiveTradingDays1_25ffcb40-925e-4406-b526-a840283f24cc" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_DebtInstrumentConvertibleThresholdConsecutiveTradingDays1"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_d627fcbc-a124-4453-b5ee-02e686640eef" xlink:to="loc_us-gaap_DebtInstrumentConvertibleThresholdConsecutiveTradingDays1_25ffcb40-925e-4406-b526-a840283f24cc" xlink:type="arc" order="27"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_NumberOfBusinessDays_6eb99a6a-c751-43c7-b5e2-a8553bba0e85" xlink:href="espr-20250630.xsd#espr_NumberOfBusinessDays"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_d627fcbc-a124-4453-b5ee-02e686640eef" xlink:to="loc_espr_NumberOfBusinessDays_6eb99a6a-c751-43c7-b5e2-a8553bba0e85" xlink:type="arc" order="28"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_NumberOfConsecutiveTradingDays_7f55a3b1-44b8-457f-be4a-896fb5098056" xlink:href="espr-20250630.xsd#espr_NumberOfConsecutiveTradingDays"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_d627fcbc-a124-4453-b5ee-02e686640eef" xlink:to="loc_espr_NumberOfConsecutiveTradingDays_7f55a3b1-44b8-457f-be4a-896fb5098056" xlink:type="arc" order="29"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_DebtInstrumentConvertibleThresholdPercentageOfLastReportedSalePrice_812a63d8-6123-4f33-b804-105dd7056196" xlink:href="espr-20250630.xsd#espr_DebtInstrumentConvertibleThresholdPercentageOfLastReportedSalePrice"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_d627fcbc-a124-4453-b5ee-02e686640eef" xlink:to="loc_espr_DebtInstrumentConvertibleThresholdPercentageOfLastReportedSalePrice_812a63d8-6123-4f33-b804-105dd7056196" xlink:type="arc" order="30"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_DebtInstrumentRedemptionOptionPeriodPriorToMaturityDateScheduledTradingDays_14ca67aa-f2dd-47d5-a901-09482ae4f447" xlink:href="espr-20250630.xsd#espr_DebtInstrumentRedemptionOptionPeriodPriorToMaturityDateScheduledTradingDays"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_d627fcbc-a124-4453-b5ee-02e686640eef" xlink:to="loc_espr_DebtInstrumentRedemptionOptionPeriodPriorToMaturityDateScheduledTradingDays_14ca67aa-f2dd-47d5-a901-09482ae4f447" xlink:type="arc" order="31"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentRedemptionPricePercentage_a1b6728c-b38d-4668-88b4-19f43f688a68" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_DebtInstrumentRedemptionPricePercentage"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_d627fcbc-a124-4453-b5ee-02e686640eef" xlink:to="loc_us-gaap_DebtInstrumentRedemptionPricePercentage_a1b6728c-b38d-4668-88b4-19f43f688a68" xlink:type="arc" order="32"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_DebtInstrumentCovenantRequiredAmountOutstanding_75c3fcb5-b748-48db-8fce-06fb85a745ee" xlink:href="espr-20250630.xsd#espr_DebtInstrumentCovenantRequiredAmountOutstanding"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_d627fcbc-a124-4453-b5ee-02e686640eef" xlink:to="loc_espr_DebtInstrumentCovenantRequiredAmountOutstanding_75c3fcb5-b748-48db-8fce-06fb85a745ee" xlink:type="arc" order="33"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtConversionConvertedInstrumentAmount1_7366cb24-9972-4420-9eb4-668aa8d7b2ad" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_DebtConversionConvertedInstrumentAmount1"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_d627fcbc-a124-4453-b5ee-02e686640eef" xlink:to="loc_us-gaap_DebtConversionConvertedInstrumentAmount1_7366cb24-9972-4420-9eb4-668aa8d7b2ad" xlink:type="arc" order="34"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_DebtInstrumentExchangeAgreementConversionWeightedAveragePricePerShareFloor_144e64fa-eccf-4772-bed2-ac8461e96e63" xlink:href="espr-20250630.xsd#espr_DebtInstrumentExchangeAgreementConversionWeightedAveragePricePerShareFloor"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_d627fcbc-a124-4453-b5ee-02e686640eef" xlink:to="loc_espr_DebtInstrumentExchangeAgreementConversionWeightedAveragePricePerShareFloor_144e64fa-eccf-4772-bed2-ac8461e96e63" xlink:type="arc" order="35"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_DebtInstrumentExchangeAgreementConvertibleThresholdTradingDays_42326c95-1697-48d3-b353-4f5653666b0f" xlink:href="espr-20250630.xsd#espr_DebtInstrumentExchangeAgreementConvertibleThresholdTradingDays"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_d627fcbc-a124-4453-b5ee-02e686640eef" xlink:to="loc_espr_DebtInstrumentExchangeAgreementConvertibleThresholdTradingDays_42326c95-1697-48d3-b353-4f5653666b0f" xlink:type="arc" order="36"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtConversionConvertedInstrumentSharesIssued1_7ca0186d-5cbf-4263-9fe2-18d55481033b" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_DebtConversionConvertedInstrumentSharesIssued1"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_d627fcbc-a124-4453-b5ee-02e686640eef" xlink:to="loc_us-gaap_DebtConversionConvertedInstrumentSharesIssued1_7ca0186d-5cbf-4263-9fe2-18d55481033b" xlink:type="arc" order="37"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RepaymentsOfConvertibleDebt_6b63f693-8002-416a-ad05-d669e2f7a233" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_RepaymentsOfConvertibleDebt"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_d627fcbc-a124-4453-b5ee-02e686640eef" xlink:to="loc_us-gaap_RepaymentsOfConvertibleDebt_6b63f693-8002-416a-ad05-d669e2f7a233" xlink:type="arc" order="38"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentRepurchasedFaceAmount_a32e3f2f-d72a-48d3-be8d-ae7eb5657efb" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_DebtInstrumentRepurchasedFaceAmount"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_d627fcbc-a124-4453-b5ee-02e686640eef" xlink:to="loc_us-gaap_DebtInstrumentRepurchasedFaceAmount_a32e3f2f-d72a-48d3-be8d-ae7eb5657efb" xlink:type="arc" order="39"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentCarryingAmount_62f31b3a-5f80-454b-856f-eaadb87a24c5" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_DebtInstrumentCarryingAmount"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_d627fcbc-a124-4453-b5ee-02e686640eef" xlink:to="loc_us-gaap_DebtInstrumentCarryingAmount_62f31b3a-5f80-454b-856f-eaadb87a24c5" xlink:type="arc" order="40"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_GainsLossesOnExtinguishmentOfDebt_0d29029f-30bd-408b-8bae-4b7fee056875" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_GainsLossesOnExtinguishmentOfDebt"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_d627fcbc-a124-4453-b5ee-02e686640eef" xlink:to="loc_us-gaap_GainsLossesOnExtinguishmentOfDebt_0d29029f-30bd-408b-8bae-4b7fee056875" xlink:type="arc" order="41"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LongTermDebt_cf0e2f3b-47c5-4b46-90b8-fb046e781244" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_LongTermDebt"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_d627fcbc-a124-4453-b5ee-02e686640eef" xlink:to="loc_us-gaap_LongTermDebt_cf0e2f3b-47c5-4b46-90b8-fb046e781244" xlink:type="arc" order="42"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentFairValue_2d39604d-9c10-4faf-919a-9e5afc36069b" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_DebtInstrumentFairValue"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_d627fcbc-a124-4453-b5ee-02e686640eef" xlink:to="loc_us-gaap_DebtInstrumentFairValue_2d39604d-9c10-4faf-919a-9e5afc36069b" xlink:type="arc" order="43"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ClassOfWarrantOrRightExercisePriceOfWarrantsOrRights1_bd508ccd-ca2e-4c33-a5a8-01e77516e540" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ClassOfWarrantOrRightExercisePriceOfWarrantsOrRights1"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_d627fcbc-a124-4453-b5ee-02e686640eef" xlink:to="loc_us-gaap_ClassOfWarrantOrRightExercisePriceOfWarrantsOrRights1_bd508ccd-ca2e-4c33-a5a8-01e77516e540" xlink:type="arc" order="44"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_ClassOfWarrantOrRightExercisePriceOfWarrantsOrRightsPremiumPercentage_39487fe8-0fb0-4e04-9f7f-347aa84abcc4" xlink:href="espr-20250630.xsd#espr_ClassOfWarrantOrRightExercisePriceOfWarrantsOrRightsPremiumPercentage"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_d627fcbc-a124-4453-b5ee-02e686640eef" xlink:to="loc_espr_ClassOfWarrantOrRightExercisePriceOfWarrantsOrRightsPremiumPercentage_39487fe8-0fb0-4e04-9f7f-347aa84abcc4" xlink:type="arc" order="45"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_TreasuryStockSharesAcquired_3a7c2d8f-7178-4ee6-8771-6cf6270b37fb" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_TreasuryStockSharesAcquired"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_d627fcbc-a124-4453-b5ee-02e686640eef" xlink:to="loc_us-gaap_TreasuryStockSharesAcquired_3a7c2d8f-7178-4ee6-8771-6cf6270b37fb" xlink:type="arc" order="46"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StockIssuedDuringPeriodSharesTreasuryStockReissued_faf72279-87e1-49ff-b5fa-3b30f1c061a8" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_StockIssuedDuringPeriodSharesTreasuryStockReissued"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_d627fcbc-a124-4453-b5ee-02e686640eef" xlink:to="loc_us-gaap_StockIssuedDuringPeriodSharesTreasuryStockReissued_faf72279-87e1-49ff-b5fa-3b30f1c061a8" xlink:type="arc" order="47"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.esperion.com/role/DebtScheduleofEstimatedFuturePrincipalPaymentsDetails" xlink:type="simple" xlink:href="espr-20250630.xsd#DebtScheduleofEstimatedFuturePrincipalPaymentsDetails"/>
  <link:definitionLink xlink:role="http://www.esperion.com/role/DebtScheduleofEstimatedFuturePrincipalPaymentsDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentLineItems_381d939e-840c-4b68-a31d-33d426321cf4" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_DebtInstrumentLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentTable_abf89ed4-bd2f-4b17-b932-9a609d96f12e" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_DebtInstrumentTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_DebtInstrumentLineItems_381d939e-840c-4b68-a31d-33d426321cf4" xlink:to="loc_us-gaap_DebtInstrumentTable_abf89ed4-bd2f-4b17-b932-9a609d96f12e" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentAxis_5abfde2d-347f-4504-9cb2-e84c3e73797b" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_DebtInstrumentAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_DebtInstrumentTable_abf89ed4-bd2f-4b17-b932-9a609d96f12e" xlink:to="loc_us-gaap_DebtInstrumentAxis_5abfde2d-347f-4504-9cb2-e84c3e73797b" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentNameDomain_5abfde2d-347f-4504-9cb2-e84c3e73797b_default" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_DebtInstrumentNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_DebtInstrumentAxis_5abfde2d-347f-4504-9cb2-e84c3e73797b" xlink:to="loc_us-gaap_DebtInstrumentNameDomain_5abfde2d-347f-4504-9cb2-e84c3e73797b_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentNameDomain_5d1d988c-f5ea-45bc-8f1d-c8385a652af1" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_DebtInstrumentNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_DebtInstrumentAxis_5abfde2d-347f-4504-9cb2-e84c3e73797b" xlink:to="loc_us-gaap_DebtInstrumentNameDomain_5d1d988c-f5ea-45bc-8f1d-c8385a652af1" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_A2025NotesAnd2030NotesMember_494a163d-9a20-4348-ad0a-568ee8ce84ce" xlink:href="espr-20250630.xsd#espr_A2025NotesAnd2030NotesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentNameDomain_5d1d988c-f5ea-45bc-8f1d-c8385a652af1" xlink:to="loc_espr_A2025NotesAnd2030NotesMember_494a163d-9a20-4348-ad0a-568ee8ce84ce" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LongTermDebtMaturitiesRepaymentsOfPrincipalRemainderOfFiscalYear_ab835047-e96f-4ae3-9180-7ce228b96d41" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_LongTermDebtMaturitiesRepaymentsOfPrincipalRemainderOfFiscalYear"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_381d939e-840c-4b68-a31d-33d426321cf4" xlink:to="loc_us-gaap_LongTermDebtMaturitiesRepaymentsOfPrincipalRemainderOfFiscalYear_ab835047-e96f-4ae3-9180-7ce228b96d41" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LongTermDebtMaturitiesRepaymentsOfPrincipalInNextTwelveMonths_069fb8bb-35f2-4cef-9027-fbb191b58e9a" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_LongTermDebtMaturitiesRepaymentsOfPrincipalInNextTwelveMonths"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_381d939e-840c-4b68-a31d-33d426321cf4" xlink:to="loc_us-gaap_LongTermDebtMaturitiesRepaymentsOfPrincipalInNextTwelveMonths_069fb8bb-35f2-4cef-9027-fbb191b58e9a" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LongTermDebtMaturitiesRepaymentsOfPrincipalInYearTwo_c7c65839-ef4c-4a42-9f09-863be830e4e5" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_LongTermDebtMaturitiesRepaymentsOfPrincipalInYearTwo"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_381d939e-840c-4b68-a31d-33d426321cf4" xlink:to="loc_us-gaap_LongTermDebtMaturitiesRepaymentsOfPrincipalInYearTwo_c7c65839-ef4c-4a42-9f09-863be830e4e5" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LongTermDebtMaturitiesRepaymentsOfPrincipalInYearThree_bd550ce5-6efc-441c-b0c8-ac5135f461c4" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_LongTermDebtMaturitiesRepaymentsOfPrincipalInYearThree"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_381d939e-840c-4b68-a31d-33d426321cf4" xlink:to="loc_us-gaap_LongTermDebtMaturitiesRepaymentsOfPrincipalInYearThree_bd550ce5-6efc-441c-b0c8-ac5135f461c4" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LongTermDebtMaturitiesRepaymentsOfPrincipalInYearFour_e4120410-af50-4297-a9c1-f63466c95648" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_LongTermDebtMaturitiesRepaymentsOfPrincipalInYearFour"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_381d939e-840c-4b68-a31d-33d426321cf4" xlink:to="loc_us-gaap_LongTermDebtMaturitiesRepaymentsOfPrincipalInYearFour_e4120410-af50-4297-a9c1-f63466c95648" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LongTermDebtMaturitiesRepaymentsOfPrincipalInYearFive_28377a32-72b6-4df1-bcbf-2e7250800057" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_LongTermDebtMaturitiesRepaymentsOfPrincipalInYearFive"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_381d939e-840c-4b68-a31d-33d426321cf4" xlink:to="loc_us-gaap_LongTermDebtMaturitiesRepaymentsOfPrincipalInYearFive_28377a32-72b6-4df1-bcbf-2e7250800057" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LongTermDebt_199d82de-8ab0-470a-886a-29a7f6f85963" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_LongTermDebt"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_381d939e-840c-4b68-a31d-33d426321cf4" xlink:to="loc_us-gaap_LongTermDebt_199d82de-8ab0-470a-886a-29a7f6f85963" xlink:type="arc" order="6"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.esperion.com/role/StockCompensationAdditionalInformationDetails" xlink:type="simple" xlink:href="espr-20250630.xsd#StockCompensationAdditionalInformationDetails"/>
  <link:definitionLink xlink:role="http://www.esperion.com/role/StockCompensationAdditionalInformationDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_04fb11fd-952c-4916-9788-cf72957e9269" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_145197e7-bf5b-4018-903e-e4187813b240" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_04fb11fd-952c-4916-9788-cf72957e9269" xlink:to="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_145197e7-bf5b-4018-903e-e4187813b240" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AwardTypeAxis_f5bf363c-db57-4f17-8d06-fd20270ecc45" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_AwardTypeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_145197e7-bf5b-4018-903e-e4187813b240" xlink:to="loc_us-gaap_AwardTypeAxis_f5bf363c-db57-4f17-8d06-fd20270ecc45" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_f5bf363c-db57-4f17-8d06-fd20270ecc45_default" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_AwardTypeAxis_f5bf363c-db57-4f17-8d06-fd20270ecc45" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_f5bf363c-db57-4f17-8d06-fd20270ecc45_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_a43ad545-caaf-424b-9beb-92ce795d5bff" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_AwardTypeAxis_f5bf363c-db57-4f17-8d06-fd20270ecc45" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_a43ad545-caaf-424b-9beb-92ce795d5bff" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EmployeeStockMember_75d9dfd9-1b45-410e-91d0-cf26943f916b" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_EmployeeStockMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_a43ad545-caaf-424b-9beb-92ce795d5bff" xlink:to="loc_us-gaap_EmployeeStockMember_75d9dfd9-1b45-410e-91d0-cf26943f916b" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EmployeeStockOptionMember_5d3c48ab-52ac-44ec-857a-29ff224a8e0a" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_EmployeeStockOptionMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_a43ad545-caaf-424b-9beb-92ce795d5bff" xlink:to="loc_us-gaap_EmployeeStockOptionMember_5d3c48ab-52ac-44ec-857a-29ff224a8e0a" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_ShareBasedPaymentArrangementOptionPerformanceBasedMember_f6e2686d-a1a8-4daa-8046-13ca3ea75e61" xlink:href="espr-20250630.xsd#espr_ShareBasedPaymentArrangementOptionPerformanceBasedMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_a43ad545-caaf-424b-9beb-92ce795d5bff" xlink:to="loc_espr_ShareBasedPaymentArrangementOptionPerformanceBasedMember_f6e2686d-a1a8-4daa-8046-13ca3ea75e61" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RestrictedStockUnitsRSUMember_a5bd25d4-3192-456a-81ed-0f05f331a19e" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_RestrictedStockUnitsRSUMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_a43ad545-caaf-424b-9beb-92ce795d5bff" xlink:to="loc_us-gaap_RestrictedStockUnitsRSUMember_a5bd25d4-3192-456a-81ed-0f05f331a19e" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PerformanceSharesMember_df6ee866-743f-40e8-8f8a-8303d0681a9c" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_PerformanceSharesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_a43ad545-caaf-424b-9beb-92ce795d5bff" xlink:to="loc_us-gaap_PerformanceSharesMember_df6ee866-743f-40e8-8f8a-8303d0681a9c" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PlanNameAxis_2987fe69-12ba-4372-b163-61f0a4490ee7" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_PlanNameAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_145197e7-bf5b-4018-903e-e4187813b240" xlink:to="loc_us-gaap_PlanNameAxis_2987fe69-12ba-4372-b163-61f0a4490ee7" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PlanNameDomain_2987fe69-12ba-4372-b163-61f0a4490ee7_default" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_PlanNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_PlanNameAxis_2987fe69-12ba-4372-b163-61f0a4490ee7" xlink:to="loc_us-gaap_PlanNameDomain_2987fe69-12ba-4372-b163-61f0a4490ee7_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PlanNameDomain_be7cc592-f878-4a64-8de4-724f7b58e424" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_PlanNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_PlanNameAxis_2987fe69-12ba-4372-b163-61f0a4490ee7" xlink:to="loc_us-gaap_PlanNameDomain_be7cc592-f878-4a64-8de4-724f7b58e424" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_StockOptionAndIncentivePlan2022Member_46df2951-0942-4cfa-8a1d-e5c8a61ac434" xlink:href="espr-20250630.xsd#espr_StockOptionAndIncentivePlan2022Member"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PlanNameDomain_be7cc592-f878-4a64-8de4-724f7b58e424" xlink:to="loc_espr_StockOptionAndIncentivePlan2022Member_46df2951-0942-4cfa-8a1d-e5c8a61ac434" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_InducementEquityPlan2017Member_c718ab91-380f-4e9c-973d-63c0ffb53066" xlink:href="espr-20250630.xsd#espr_InducementEquityPlan2017Member"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PlanNameDomain_be7cc592-f878-4a64-8de4-724f7b58e424" xlink:to="loc_espr_InducementEquityPlan2017Member_c718ab91-380f-4e9c-973d-63c0ffb53066" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAuthorized_2a72b13a-3cdc-42f4-a85d-31a6a61f3ad3" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAuthorized"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_04fb11fd-952c-4916-9788-cf72957e9269" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAuthorized_2a72b13a-3cdc-42f4-a85d-31a6a61f3ad3" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_EmployeeStockPurchasePlanMaximumAnnualContributionsPerEmployeePercent_dfc82e07-6435-4ade-9504-84bb9a3e5ad9" xlink:href="espr-20250630.xsd#espr_EmployeeStockPurchasePlanMaximumAnnualContributionsPerEmployeePercent"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_04fb11fd-952c-4916-9788-cf72957e9269" xlink:to="loc_espr_EmployeeStockPurchasePlanMaximumAnnualContributionsPerEmployeePercent_dfc82e07-6435-4ade-9504-84bb9a3e5ad9" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_EmployeeStockPurchasePlanMaximumAnnualContributionsPerEmployeeAmount_48823b3b-3150-435b-8b45-8893f4479298" xlink:href="espr-20250630.xsd#espr_EmployeeStockPurchasePlanMaximumAnnualContributionsPerEmployeeAmount"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_04fb11fd-952c-4916-9788-cf72957e9269" xlink:to="loc_espr_EmployeeStockPurchasePlanMaximumAnnualContributionsPerEmployeeAmount_48823b3b-3150-435b-8b45-8893f4479298" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_EmployeeStockPurchasePlanPercentageDiscountOnShares_2a9fc1df-7b37-4d04-a8d4-b9ef95042927" xlink:href="espr-20250630.xsd#espr_EmployeeStockPurchasePlanPercentageDiscountOnShares"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_04fb11fd-952c-4916-9788-cf72957e9269" xlink:to="loc_espr_EmployeeStockPurchasePlanPercentageDiscountOnShares_2a9fc1df-7b37-4d04-a8d4-b9ef95042927" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_EmployeeStockPurchasePlanDurationOfOfferingPeriod_08e9b10f-ca00-43fe-8b32-08e8cdc6c9c3" xlink:href="espr-20250630.xsd#espr_EmployeeStockPurchasePlanDurationOfOfferingPeriod"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_04fb11fd-952c-4916-9788-cf72957e9269" xlink:to="loc_espr_EmployeeStockPurchasePlanDurationOfOfferingPeriod_08e9b10f-ca00-43fe-8b32-08e8cdc6c9c3" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AllocatedShareBasedCompensationExpense_7d5f00d1-fd6e-46f5-b64c-5c6535e2af2d" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_AllocatedShareBasedCompensationExpense"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_04fb11fd-952c-4916-9788-cf72957e9269" xlink:to="loc_us-gaap_AllocatedShareBasedCompensationExpense_7d5f00d1-fd6e-46f5-b64c-5c6535e2af2d" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_CommonStockCapitalSharesReservedForFutureIssuanceIncrease_fecfec53-c5c9-4f67-9571-c940aa875e77" xlink:href="espr-20250630.xsd#espr_CommonStockCapitalSharesReservedForFutureIssuanceIncrease"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_04fb11fd-952c-4916-9788-cf72957e9269" xlink:to="loc_espr_CommonStockCapitalSharesReservedForFutureIssuanceIncrease_fecfec53-c5c9-4f67-9571-c940aa875e77" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardSharesIssuedInPeriod_d29f8627-36ed-4b0f-8fc8-766636c36879" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardSharesIssuedInPeriod"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_04fb11fd-952c-4916-9788-cf72957e9269" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardSharesIssuedInPeriod_d29f8627-36ed-4b0f-8fc8-766636c36879" xlink:type="arc" order="7"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CommonStockCapitalSharesReservedForFutureIssuance_d7dd997f-0bee-4fff-b460-e9584f188a36" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_CommonStockCapitalSharesReservedForFutureIssuance"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_04fb11fd-952c-4916-9788-cf72957e9269" xlink:to="loc_us-gaap_CommonStockCapitalSharesReservedForFutureIssuance_d7dd997f-0bee-4fff-b460-e9584f188a36" xlink:type="arc" order="8"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsCapitalizedAmount_0d335eea-1327-4b5d-ba47-af9481f56781" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_EmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsCapitalizedAmount"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_04fb11fd-952c-4916-9788-cf72957e9269" xlink:to="loc_us-gaap_EmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsCapitalizedAmount_0d335eea-1327-4b5d-ba47-af9481f56781" xlink:type="arc" order="9"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedStockOptions_c8f0f5c9-4bb5-4749-abf2-4267487469c0" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedStockOptions"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_04fb11fd-952c-4916-9788-cf72957e9269" xlink:to="loc_us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedStockOptions_c8f0f5c9-4bb5-4749-abf2-4267487469c0" xlink:type="arc" order="10"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1_c5c37d29-0501-48a6-a8e9-5c3fe4dcf60c" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_04fb11fd-952c-4916-9788-cf72957e9269" xlink:to="loc_us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1_c5c37d29-0501-48a6-a8e9-5c3fe4dcf60c" xlink:type="arc" order="11"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedShareBasedAwardsOtherThanOptions_89a29ed7-5032-4f5f-a24f-fcce762cb2e9" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedShareBasedAwardsOtherThanOptions"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_04fb11fd-952c-4916-9788-cf72957e9269" xlink:to="loc_us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedShareBasedAwardsOtherThanOptions_89a29ed7-5032-4f5f-a24f-fcce762cb2e9" xlink:type="arc" order="12"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.esperion.com/role/StockCompensationPBSOsDetails" xlink:type="simple" xlink:href="espr-20250630.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_7e5d3705-3d57-4edc-9007-caf700b00dbc" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_a945f386-7506-40bb-ae21-01a67cd96df4" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_7e5d3705-3d57-4edc-9007-caf700b00dbc" xlink:to="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_a945f386-7506-40bb-ae21-01a67cd96df4" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AwardTypeAxis_dcfa132f-c2cd-442e-9fcb-bb4d880fa56a" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_AwardTypeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_a945f386-7506-40bb-ae21-01a67cd96df4" xlink:to="loc_us-gaap_AwardTypeAxis_dcfa132f-c2cd-442e-9fcb-bb4d880fa56a" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_dcfa132f-c2cd-442e-9fcb-bb4d880fa56a_default" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_AwardTypeAxis_dcfa132f-c2cd-442e-9fcb-bb4d880fa56a" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_dcfa132f-c2cd-442e-9fcb-bb4d880fa56a_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_76dece32-b473-4780-9552-8d2e897db6a1" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_AwardTypeAxis_dcfa132f-c2cd-442e-9fcb-bb4d880fa56a" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_76dece32-b473-4780-9552-8d2e897db6a1" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_ShareBasedPaymentArrangementOptionPerformanceBasedMember_7f32caba-97a9-444c-88f3-0d5a287a1833" xlink:href="espr-20250630.xsd#espr_ShareBasedPaymentArrangementOptionPerformanceBasedMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_76dece32-b473-4780-9552-8d2e897db6a1" xlink:to="loc_espr_ShareBasedPaymentArrangementOptionPerformanceBasedMember_7f32caba-97a9-444c-88f3-0d5a287a1833" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingRollForward_e657d79c-6d41-49bc-847c-f75042f96465" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingRollForward"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_7e5d3705-3d57-4edc-9007-caf700b00dbc" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingRollForward_e657d79c-6d41-49bc-847c-f75042f96465" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingNumber_16418e0c-4e51-4ffc-898e-2cf8be723f3e" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingNumber"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingRollForward_e657d79c-6d41-49bc-847c-f75042f96465" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingNumber_16418e0c-4e51-4ffc-898e-2cf8be723f3e" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsGrantsInPeriodGross_e963b7f2-f56d-45df-a3ae-4190cde24a67" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsGrantsInPeriodGross"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingRollForward_e657d79c-6d41-49bc-847c-f75042f96465" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsGrantsInPeriodGross_e963b7f2-f56d-45df-a3ae-4190cde24a67" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsForfeituresAndExpirationsInPeriod_b24410fa-2eec-459e-83a0-d29fb18cb9fa" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsForfeituresAndExpirationsInPeriod"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingRollForward_e657d79c-6d41-49bc-847c-f75042f96465" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsForfeituresAndExpirationsInPeriod_b24410fa-2eec-459e-83a0-d29fb18cb9fa" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StockIssuedDuringPeriodSharesStockOptionsExercised_e3f11dea-e8bd-46d4-ac22-23917d134b2f" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_StockIssuedDuringPeriodSharesStockOptionsExercised"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingRollForward_e657d79c-6d41-49bc-847c-f75042f96465" xlink:to="loc_us-gaap_StockIssuedDuringPeriodSharesStockOptionsExercised_e3f11dea-e8bd-46d4-ac22-23917d134b2f" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingNumber_dfd9075b-13c9-4608-ad6e-50e9fd891647" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingNumber"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsVestedAndExpectedToVestOutstandingNumber_da0361e1-8eb9-458a-af87-940c7f55ad29" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsVestedAndExpectedToVestOutstandingNumber"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_7e5d3705-3d57-4edc-9007-caf700b00dbc" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsVestedAndExpectedToVestOutstandingNumber_da0361e1-8eb9-458a-af87-940c7f55ad29" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsExercisableNumber_97c5aa28-aa0c-41a6-adfe-affa82e73bc5" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsExercisableNumber"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_7e5d3705-3d57-4edc-9007-caf700b00dbc" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsExercisableNumber_97c5aa28-aa0c-41a6-adfe-affa82e73bc5" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingWeightedAverageExercisePriceRollforward_59af532d-5d2f-433f-9cdb-59faf24ce46b" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingWeightedAverageExercisePriceRollforward"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_7e5d3705-3d57-4edc-9007-caf700b00dbc" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingWeightedAverageExercisePriceRollforward_59af532d-5d2f-433f-9cdb-59faf24ce46b" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingWeightedAverageExercisePrice_3d622921-8164-4cf9-883c-7b7193c72298" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingWeightedAverageExercisePrice"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingWeightedAverageExercisePriceRollforward_59af532d-5d2f-433f-9cdb-59faf24ce46b" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingWeightedAverageExercisePrice_3d622921-8164-4cf9-883c-7b7193c72298" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardOptionsGrantsInPeriodWeightedAverageExercisePrice_71078259-7cfe-4fa0-94ec-a204ef391bc4" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardOptionsGrantsInPeriodWeightedAverageExercisePrice"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingWeightedAverageExercisePriceRollforward_59af532d-5d2f-433f-9cdb-59faf24ce46b" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardOptionsGrantsInPeriodWeightedAverageExercisePrice_71078259-7cfe-4fa0-94ec-a204ef391bc4" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsForfeituresAndExpirationsInPeriodWeightedAverageExercisePrice_3c9ac778-ac11-4db0-9529-7f6da07a1f5d" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsForfeituresAndExpirationsInPeriodWeightedAverageExercisePrice"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingWeightedAverageExercisePriceRollforward_59af532d-5d2f-433f-9cdb-59faf24ce46b" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsForfeituresAndExpirationsInPeriodWeightedAverageExercisePrice_3c9ac778-ac11-4db0-9529-7f6da07a1f5d" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardOptionsExercisesInPeriodWeightedAverageExercisePrice_734804bf-f7fc-4a45-b335-27bacec8fb55" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardOptionsExercisesInPeriodWeightedAverageExercisePrice"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingWeightedAverageExercisePriceRollforward_59af532d-5d2f-433f-9cdb-59faf24ce46b" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardOptionsExercisesInPeriodWeightedAverageExercisePrice_734804bf-f7fc-4a45-b335-27bacec8fb55" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingWeightedAverageExercisePrice_451918f5-8282-4a7b-877a-8ef20261c819" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingWeightedAverageExercisePrice"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsVestedAndExpectedToVestOutstandingWeightedAverageExercisePrice_18ccde3b-ebdb-45aa-b4d1-678bb0f0fe68" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsVestedAndExpectedToVestOutstandingWeightedAverageExercisePrice"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_7e5d3705-3d57-4edc-9007-caf700b00dbc" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsVestedAndExpectedToVestOutstandingWeightedAverageExercisePrice_18ccde3b-ebdb-45aa-b4d1-678bb0f0fe68" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsExercisableWeightedAverageExercisePrice_9d329561-e7a0-40c6-a93d-6af484bd1a0d" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsExercisableWeightedAverageExercisePrice"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_7e5d3705-3d57-4edc-9007-caf700b00dbc" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsExercisableWeightedAverageExercisePrice_9d329561-e7a0-40c6-a93d-6af484bd1a0d" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsWeightedAverageRemainingContractualTermAbstract_401f9e41-fcb3-4dcf-a591-dff9094bfbf4" xlink:href="espr-20250630.xsd#espr_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsWeightedAverageRemainingContractualTermAbstract"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_7e5d3705-3d57-4edc-9007-caf700b00dbc" xlink:to="loc_espr_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsWeightedAverageRemainingContractualTermAbstract_401f9e41-fcb3-4dcf-a591-dff9094bfbf4" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardOptionsOutstandingWeightedAverageRemainingContractualTerm2_538a08a3-3566-449b-87b0-5ce077e51b5f" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardOptionsOutstandingWeightedAverageRemainingContractualTerm2"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_espr_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsWeightedAverageRemainingContractualTermAbstract_401f9e41-fcb3-4dcf-a591-dff9094bfbf4" xlink:to="loc_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardOptionsOutstandingWeightedAverageRemainingContractualTerm2_538a08a3-3566-449b-87b0-5ce077e51b5f" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardOptionsVestedAndExpectedToVestOutstandingWeightedAverageRemainingContractualTerm1_d3890be9-c3e1-4317-abff-e28471500d89" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardOptionsVestedAndExpectedToVestOutstandingWeightedAverageRemainingContractualTerm1"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_espr_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsWeightedAverageRemainingContractualTermAbstract_401f9e41-fcb3-4dcf-a591-dff9094bfbf4" xlink:to="loc_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardOptionsVestedAndExpectedToVestOutstandingWeightedAverageRemainingContractualTerm1_d3890be9-c3e1-4317-abff-e28471500d89" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardOptionsExercisableWeightedAverageRemainingContractualTerm1_dda4e040-b493-499a-94ed-3b303091dccf" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardOptionsExercisableWeightedAverageRemainingContractualTerm1"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_espr_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsWeightedAverageRemainingContractualTermAbstract_401f9e41-fcb3-4dcf-a591-dff9094bfbf4" xlink:to="loc_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardOptionsExercisableWeightedAverageRemainingContractualTerm1_dda4e040-b493-499a-94ed-3b303091dccf" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_ShareBasedCompensationArrangementByShareBasedPaymentAwardAggregateIntrinsicValueAbstract_24a158ae-1559-470a-8cce-8111c50535d8" xlink:href="espr-20250630.xsd#espr_ShareBasedCompensationArrangementByShareBasedPaymentAwardAggregateIntrinsicValueAbstract"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_7e5d3705-3d57-4edc-9007-caf700b00dbc" xlink:to="loc_espr_ShareBasedCompensationArrangementByShareBasedPaymentAwardAggregateIntrinsicValueAbstract_24a158ae-1559-470a-8cce-8111c50535d8" xlink:type="arc" order="7"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingIntrinsicValue_b10b4cd9-a472-4d93-a586-79803525718d" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingIntrinsicValue"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_espr_ShareBasedCompensationArrangementByShareBasedPaymentAwardAggregateIntrinsicValueAbstract_24a158ae-1559-470a-8cce-8111c50535d8" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingIntrinsicValue_b10b4cd9-a472-4d93-a586-79803525718d" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsVestedAndExpectedToVestOutstandingAggregateIntrinsicValue_270fe7ef-8e4b-4163-86a6-a535d2c937d4" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsVestedAndExpectedToVestOutstandingAggregateIntrinsicValue"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_espr_ShareBasedCompensationArrangementByShareBasedPaymentAwardAggregateIntrinsicValueAbstract_24a158ae-1559-470a-8cce-8111c50535d8" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsVestedAndExpectedToVestOutstandingAggregateIntrinsicValue_270fe7ef-8e4b-4163-86a6-a535d2c937d4" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardOptionsExercisableIntrinsicValue1_8b146d63-51a8-4eb3-a568-6843519a66bc" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardOptionsExercisableIntrinsicValue1"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_espr_ShareBasedCompensationArrangementByShareBasedPaymentAwardAggregateIntrinsicValueAbstract_24a158ae-1559-470a-8cce-8111c50535d8" xlink:to="loc_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardOptionsExercisableIntrinsicValue1_8b146d63-51a8-4eb3-a568-6843519a66bc" xlink:type="arc" order="3"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.esperion.com/role/StockCompensationRSUsDetails" xlink:type="simple" xlink:href="espr-20250630.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_9b285f23-378a-4a7e-99c9-a1051518ba56" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_b9dd9f26-609f-45a6-94cc-77c127b4b519" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_9b285f23-378a-4a7e-99c9-a1051518ba56" xlink:to="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_b9dd9f26-609f-45a6-94cc-77c127b4b519" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AwardTypeAxis_bdde9560-ae97-4854-bf53-5b98ac3da0dd" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_AwardTypeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_b9dd9f26-609f-45a6-94cc-77c127b4b519" xlink:to="loc_us-gaap_AwardTypeAxis_bdde9560-ae97-4854-bf53-5b98ac3da0dd" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_bdde9560-ae97-4854-bf53-5b98ac3da0dd_default" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_AwardTypeAxis_bdde9560-ae97-4854-bf53-5b98ac3da0dd" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_bdde9560-ae97-4854-bf53-5b98ac3da0dd_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_a0b9d045-cf2c-48a7-9093-3f6bcb2c8f34" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_AwardTypeAxis_bdde9560-ae97-4854-bf53-5b98ac3da0dd" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_a0b9d045-cf2c-48a7-9093-3f6bcb2c8f34" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RestrictedStockUnitsRSUMember_bc2bebbd-d494-41c0-82bf-fa1dee64bace" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_RestrictedStockUnitsRSUMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_a0b9d045-cf2c-48a7-9093-3f6bcb2c8f34" xlink:to="loc_us-gaap_RestrictedStockUnitsRSUMember_bc2bebbd-d494-41c0-82bf-fa1dee64bace" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedRollForward_6f7b74e1-8981-444d-83f4-348ed2843276" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedRollForward"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_9b285f23-378a-4a7e-99c9-a1051518ba56" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedRollForward_6f7b74e1-8981-444d-83f4-348ed2843276" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedNumber_a3f53fda-6ce7-4996-832a-bac9c89cf8f3" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedNumber"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedRollForward_6f7b74e1-8981-444d-83f4-348ed2843276" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedNumber_a3f53fda-6ce7-4996-832a-bac9c89cf8f3" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsGrantsInPeriod_c30bd9be-43da-4e3d-bc1a-7523634229cb" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsGrantsInPeriod"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedRollForward_6f7b74e1-8981-444d-83f4-348ed2843276" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsGrantsInPeriod_c30bd9be-43da-4e3d-bc1a-7523634229cb" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsForfeitedInPeriod_e86b0881-d787-4195-8958-aa84bf449c8e" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsForfeitedInPeriod"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedRollForward_6f7b74e1-8981-444d-83f4-348ed2843276" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsForfeitedInPeriod_e86b0881-d787-4195-8958-aa84bf449c8e" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsVestedInPeriod_38b221ca-8fb2-47fe-82c9-c3ed566a738d" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsVestedInPeriod"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedRollForward_6f7b74e1-8981-444d-83f4-348ed2843276" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsVestedInPeriod_38b221ca-8fb2-47fe-82c9-c3ed566a738d" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedNumber_ec288dbc-453e-4aed-8a0a-0ddef44bcd37" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedNumber"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValueRollForward_cd628170-51d1-4d9e-b83c-219309202759" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValueRollForward"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_9b285f23-378a-4a7e-99c9-a1051518ba56" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValueRollForward_cd628170-51d1-4d9e-b83c-219309202759" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValue_d7f037d4-5fec-4ce9-8b2d-e942ed989412" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValue"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValueRollForward_cd628170-51d1-4d9e-b83c-219309202759" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValue_d7f037d4-5fec-4ce9-8b2d-e942ed989412" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsGrantsInPeriodWeightedAverageGrantDateFairValue_9bc3fb94-518c-41bf-b658-d07546b3040c" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsGrantsInPeriodWeightedAverageGrantDateFairValue"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValueRollForward_cd628170-51d1-4d9e-b83c-219309202759" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsGrantsInPeriodWeightedAverageGrantDateFairValue_9bc3fb94-518c-41bf-b658-d07546b3040c" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsForfeituresWeightedAverageGrantDateFairValue_439dc84f-1443-40b9-b7cb-3e3d5f257ff2" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsForfeituresWeightedAverageGrantDateFairValue"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValueRollForward_cd628170-51d1-4d9e-b83c-219309202759" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsForfeituresWeightedAverageGrantDateFairValue_439dc84f-1443-40b9-b7cb-3e3d5f257ff2" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsVestedInPeriodWeightedAverageGrantDateFairValue_fa16add3-2da9-4c7e-97ae-c78363b38571" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsVestedInPeriodWeightedAverageGrantDateFairValue"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValueRollForward_cd628170-51d1-4d9e-b83c-219309202759" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsVestedInPeriodWeightedAverageGrantDateFairValue_fa16add3-2da9-4c7e-97ae-c78363b38571" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValue_21290e3c-51f0-4256-a7e9-3edf07274a3d" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValue"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.esperion.com/role/StockCompensationSummaryofTotalStockBasedCompensationExpenseDetails" xlink:type="simple" xlink:href="espr-20250630.xsd#StockCompensationSummaryofTotalStockBasedCompensationExpenseDetails"/>
  <link:definitionLink xlink:role="http://www.esperion.com/role/StockCompensationSummaryofTotalStockBasedCompensationExpenseDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_df0145dd-bdff-404b-b01a-48ca3e1c1eb7" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_0f661a23-548b-4a5c-9529-a57861ca9530" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_df0145dd-bdff-404b-b01a-48ca3e1c1eb7" xlink:to="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_0f661a23-548b-4a5c-9529-a57861ca9530" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncomeStatementLocationAxis_f83b7d9d-e754-4e28-8547-53f83fd1c033" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_IncomeStatementLocationAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_0f661a23-548b-4a5c-9529-a57861ca9530" xlink:to="loc_us-gaap_IncomeStatementLocationAxis_f83b7d9d-e754-4e28-8547-53f83fd1c033" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncomeStatementLocationDomain_f83b7d9d-e754-4e28-8547-53f83fd1c033_default" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_IncomeStatementLocationDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_IncomeStatementLocationAxis_f83b7d9d-e754-4e28-8547-53f83fd1c033" xlink:to="loc_us-gaap_IncomeStatementLocationDomain_f83b7d9d-e754-4e28-8547-53f83fd1c033_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncomeStatementLocationDomain_add0cc1c-4d15-4b18-9b08-766125e69185" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_IncomeStatementLocationDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_IncomeStatementLocationAxis_f83b7d9d-e754-4e28-8547-53f83fd1c033" xlink:to="loc_us-gaap_IncomeStatementLocationDomain_add0cc1c-4d15-4b18-9b08-766125e69185" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ResearchAndDevelopmentExpenseMember_d3ce5504-c649-437b-891c-c28ccbbf895e" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ResearchAndDevelopmentExpenseMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncomeStatementLocationDomain_add0cc1c-4d15-4b18-9b08-766125e69185" xlink:to="loc_us-gaap_ResearchAndDevelopmentExpenseMember_d3ce5504-c649-437b-891c-c28ccbbf895e" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SellingAndMarketingExpenseMember_f55ac557-6ff8-4a51-9d60-1ce66ff26c6e" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_SellingAndMarketingExpenseMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncomeStatementLocationDomain_add0cc1c-4d15-4b18-9b08-766125e69185" xlink:to="loc_us-gaap_SellingAndMarketingExpenseMember_f55ac557-6ff8-4a51-9d60-1ce66ff26c6e" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AllocatedShareBasedCompensationExpense_290ae9f5-a39f-4fd4-b2b1-014c75fe3d7c" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_AllocatedShareBasedCompensationExpense"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_df0145dd-bdff-404b-b01a-48ca3e1c1eb7" xlink:to="loc_us-gaap_AllocatedShareBasedCompensationExpense_290ae9f5-a39f-4fd4-b2b1-014c75fe3d7c" xlink:type="arc" order="0"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.esperion.com/role/SegmentReportingDetails" xlink:type="simple" xlink:href="espr-20250630.xsd#SegmentReportingDetails"/>
  <link:definitionLink xlink:role="http://www.esperion.com/role/SegmentReportingDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SegmentReportingInformationLineItems_cd5156ab-34f7-4918-85e7-d4bd1875325f" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_SegmentReportingInformationLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfSegmentReportingInformationBySegmentTable_dc698a47-f0b5-4f3c-9282-982e13b86625" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ScheduleOfSegmentReportingInformationBySegmentTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_SegmentReportingInformationLineItems_cd5156ab-34f7-4918-85e7-d4bd1875325f" xlink:to="loc_us-gaap_ScheduleOfSegmentReportingInformationBySegmentTable_dc698a47-f0b5-4f3c-9282-982e13b86625" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductOrServiceAxis_23455bf9-7139-4cc7-bc07-40fba8f20a4c" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_ProductOrServiceAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfSegmentReportingInformationBySegmentTable_dc698a47-f0b5-4f3c-9282-982e13b86625" xlink:to="loc_srt_ProductOrServiceAxis_23455bf9-7139-4cc7-bc07-40fba8f20a4c" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductsAndServicesDomain_23455bf9-7139-4cc7-bc07-40fba8f20a4c_default" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_ProductsAndServicesDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_ProductOrServiceAxis_23455bf9-7139-4cc7-bc07-40fba8f20a4c" xlink:to="loc_srt_ProductsAndServicesDomain_23455bf9-7139-4cc7-bc07-40fba8f20a4c_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductsAndServicesDomain_ca5bb466-c72a-4544-95b2-d07c256fa9f1" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_ProductsAndServicesDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_ProductOrServiceAxis_23455bf9-7139-4cc7-bc07-40fba8f20a4c" xlink:to="loc_srt_ProductsAndServicesDomain_ca5bb466-c72a-4544-95b2-d07c256fa9f1" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ProductMember_e9ab4b92-c936-45c8-be3b-1efc2235db94" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ProductMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ProductsAndServicesDomain_ca5bb466-c72a-4544-95b2-d07c256fa9f1" xlink:to="loc_us-gaap_ProductMember_e9ab4b92-c936-45c8-be3b-1efc2235db94" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_CollaborationRevenueMember_b64896ec-2b0a-493e-8ee0-69054d8809a3" xlink:href="espr-20250630.xsd#espr_CollaborationRevenueMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ProductsAndServicesDomain_ca5bb466-c72a-4544-95b2-d07c256fa9f1" xlink:to="loc_espr_CollaborationRevenueMember_b64896ec-2b0a-493e-8ee0-69054d8809a3" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_NumberOfReportableSegments_54f88c0c-1c19-48af-80c5-f0577cf13634" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_NumberOfReportableSegments"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SegmentReportingInformationLineItems_cd5156ab-34f7-4918-85e7-d4bd1875325f" xlink:to="loc_us-gaap_NumberOfReportableSegments_54f88c0c-1c19-48af-80c5-f0577cf13634" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax_8bb4d555-a1ab-4a02-9647-dc31863093b4" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SegmentReportingInformationLineItems_cd5156ab-34f7-4918-85e7-d4bd1875325f" xlink:to="loc_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax_8bb4d555-a1ab-4a02-9647-dc31863093b4" xlink:type="arc" order="1"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.esperion.com/role/StockholdersDeficitDetails" xlink:type="simple" xlink:href="espr-20250630.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_6e037202-6438-4b22-90bd-fff653cafda2" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_SubsidiarySaleOfStockLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SubsidiaryOrEquityMethodInvesteeSaleOfStockBySubsidiaryOrEquityInvesteeTable_fc96482e-343d-4c27-8968-a0380a0e352a" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_SubsidiaryOrEquityMethodInvesteeSaleOfStockBySubsidiaryOrEquityInvesteeTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_SubsidiarySaleOfStockLineItems_6e037202-6438-4b22-90bd-fff653cafda2" xlink:to="loc_us-gaap_SubsidiaryOrEquityMethodInvesteeSaleOfStockBySubsidiaryOrEquityInvesteeTable_fc96482e-343d-4c27-8968-a0380a0e352a" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SubsidiarySaleOfStockAxis_679a6bcf-d5e9-4b4e-9a6d-f309ee328450" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_SubsidiarySaleOfStockAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_SubsidiaryOrEquityMethodInvesteeSaleOfStockBySubsidiaryOrEquityInvesteeTable_fc96482e-343d-4c27-8968-a0380a0e352a" xlink:to="loc_us-gaap_SubsidiarySaleOfStockAxis_679a6bcf-d5e9-4b4e-9a6d-f309ee328450" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SaleOfStockNameOfTransactionDomain_679a6bcf-d5e9-4b4e-9a6d-f309ee328450_default" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_SaleOfStockNameOfTransactionDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_SubsidiarySaleOfStockAxis_679a6bcf-d5e9-4b4e-9a6d-f309ee328450" xlink:to="loc_us-gaap_SaleOfStockNameOfTransactionDomain_679a6bcf-d5e9-4b4e-9a6d-f309ee328450_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SaleOfStockNameOfTransactionDomain_acea195c-6058-49f0-9d93-0c7f70dd006e" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_SaleOfStockNameOfTransactionDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_SubsidiarySaleOfStockAxis_679a6bcf-d5e9-4b4e-9a6d-f309ee328450" xlink:to="loc_us-gaap_SaleOfStockNameOfTransactionDomain_acea195c-6058-49f0-9d93-0c7f70dd006e" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_CommitmentOfferingMember_79d31736-47da-4791-afde-68b19656502a" xlink:href="espr-20250630.xsd#espr_CommitmentOfferingMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SaleOfStockNameOfTransactionDomain_acea195c-6058-49f0-9d93-0c7f70dd006e" xlink:to="loc_espr_CommitmentOfferingMember_79d31736-47da-4791-afde-68b19656502a" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OverAllotmentOptionMember_b97ce09e-8679-452c-8165-116127d20808" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_OverAllotmentOptionMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SaleOfStockNameOfTransactionDomain_acea195c-6058-49f0-9d93-0c7f70dd006e" xlink:to="loc_us-gaap_OverAllotmentOptionMember_b97ce09e-8679-452c-8165-116127d20808" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_AtTheMarketProgramMember_b9d97c76-78ea-4de9-8819-034933c73ff7" xlink:href="espr-20250630.xsd#espr_AtTheMarketProgramMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SaleOfStockNameOfTransactionDomain_acea195c-6058-49f0-9d93-0c7f70dd006e" xlink:to="loc_espr_AtTheMarketProgramMember_b9d97c76-78ea-4de9-8819-034933c73ff7" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_TypeOfArrangementAxis_8d5cf71f-93c6-4565-870a-afaf55266051" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_TypeOfArrangementAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_SubsidiaryOrEquityMethodInvesteeSaleOfStockBySubsidiaryOrEquityInvesteeTable_fc96482e-343d-4c27-8968-a0380a0e352a" xlink:to="loc_us-gaap_TypeOfArrangementAxis_8d5cf71f-93c6-4565-870a-afaf55266051" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ArrangementsAndNonarrangementTransactionsMember_8d5cf71f-93c6-4565-870a-afaf55266051_default" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ArrangementsAndNonarrangementTransactionsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_TypeOfArrangementAxis_8d5cf71f-93c6-4565-870a-afaf55266051" xlink:to="loc_us-gaap_ArrangementsAndNonarrangementTransactionsMember_8d5cf71f-93c6-4565-870a-afaf55266051_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ArrangementsAndNonarrangementTransactionsMember_5326a251-d40a-466e-9a41-730352e028fc" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ArrangementsAndNonarrangementTransactionsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_TypeOfArrangementAxis_8d5cf71f-93c6-4565-870a-afaf55266051" xlink:to="loc_us-gaap_ArrangementsAndNonarrangementTransactionsMember_5326a251-d40a-466e-9a41-730352e028fc" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_WainwrightMember_6cd3e111-3ae9-4e14-87b4-9b58e049ac04" xlink:href="espr-20250630.xsd#espr_WainwrightMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ArrangementsAndNonarrangementTransactionsMember_5326a251-d40a-466e-9a41-730352e028fc" xlink:to="loc_espr_WainwrightMember_6cd3e111-3ae9-4e14-87b4-9b58e049ac04" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_WarrantAmendmentAgreementsMember_b104e653-684a-4f81-81ea-b50955de0d1e" xlink:href="espr-20250630.xsd#espr_WarrantAmendmentAgreementsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ArrangementsAndNonarrangementTransactionsMember_5326a251-d40a-466e-9a41-730352e028fc" xlink:to="loc_espr_WarrantAmendmentAgreementsMember_b104e653-684a-4f81-81ea-b50955de0d1e" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_SecuritiesPurchaseAgreementMember_20e0e9be-281a-4621-a31e-c0322b8f8ba5" xlink:href="espr-20250630.xsd#espr_SecuritiesPurchaseAgreementMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ArrangementsAndNonarrangementTransactionsMember_5326a251-d40a-466e-9a41-730352e028fc" xlink:to="loc_espr_SecuritiesPurchaseAgreementMember_20e0e9be-281a-4621-a31e-c0322b8f8ba5" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ClassOfWarrantOrRightAxis_de3a4c2d-0d35-49c1-9de1-e5d09ba80d5d" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ClassOfWarrantOrRightAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_SubsidiaryOrEquityMethodInvesteeSaleOfStockBySubsidiaryOrEquityInvesteeTable_fc96482e-343d-4c27-8968-a0380a0e352a" xlink:to="loc_us-gaap_ClassOfWarrantOrRightAxis_de3a4c2d-0d35-49c1-9de1-e5d09ba80d5d" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ClassOfWarrantOrRightDomain_de3a4c2d-0d35-49c1-9de1-e5d09ba80d5d_default" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ClassOfWarrantOrRightDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_ClassOfWarrantOrRightAxis_de3a4c2d-0d35-49c1-9de1-e5d09ba80d5d" xlink:to="loc_us-gaap_ClassOfWarrantOrRightDomain_de3a4c2d-0d35-49c1-9de1-e5d09ba80d5d_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ClassOfWarrantOrRightDomain_e1cea1c5-d12a-46e9-a66b-79ad19a89123" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ClassOfWarrantOrRightDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_ClassOfWarrantOrRightAxis_de3a4c2d-0d35-49c1-9de1-e5d09ba80d5d" xlink:to="loc_us-gaap_ClassOfWarrantOrRightDomain_e1cea1c5-d12a-46e9-a66b-79ad19a89123" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_CommonStockAndAccompanyingWarrantMember_f50c712d-dd6e-4bab-a0b5-6c28c4e3e82a" xlink:href="espr-20250630.xsd#espr_CommonStockAndAccompanyingWarrantMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfWarrantOrRightDomain_e1cea1c5-d12a-46e9-a66b-79ad19a89123" xlink:to="loc_espr_CommonStockAndAccompanyingWarrantMember_f50c712d-dd6e-4bab-a0b5-6c28c4e3e82a" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_TheWarrantsMember_15c137cc-7d87-4da0-afcd-6098373ab645" xlink:href="espr-20250630.xsd#espr_TheWarrantsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfWarrantOrRightDomain_e1cea1c5-d12a-46e9-a66b-79ad19a89123" xlink:to="loc_espr_TheWarrantsMember_15c137cc-7d87-4da0-afcd-6098373ab645" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_PreFundedWarrantAndAccompanyingWarrantMember_23ec80a7-decc-4cc0-8f75-26bfa8d05a57" xlink:href="espr-20250630.xsd#espr_PreFundedWarrantAndAccompanyingWarrantMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfWarrantOrRightDomain_e1cea1c5-d12a-46e9-a66b-79ad19a89123" xlink:to="loc_espr_PreFundedWarrantAndAccompanyingWarrantMember_23ec80a7-decc-4cc0-8f75-26bfa8d05a57" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_PreFundedWarrantMember_7032deec-72dc-44f6-b8de-c47ae396aa49" xlink:href="espr-20250630.xsd#espr_PreFundedWarrantMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfWarrantOrRightDomain_e1cea1c5-d12a-46e9-a66b-79ad19a89123" xlink:to="loc_espr_PreFundedWarrantMember_7032deec-72dc-44f6-b8de-c47ae396aa49" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_WarrantsMember_f8fd8446-8230-4fd7-be43-fe89b0ff515f" xlink:href="espr-20250630.xsd#espr_WarrantsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfWarrantOrRightDomain_e1cea1c5-d12a-46e9-a66b-79ad19a89123" xlink:to="loc_espr_WarrantsMember_f8fd8446-8230-4fd7-be43-fe89b0ff515f" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SaleOfStockNumberOfSharesIssuedInTransaction_83ef8aaa-891b-41d1-a622-244ef60d9d5e" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_SaleOfStockNumberOfSharesIssuedInTransaction"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SubsidiarySaleOfStockLineItems_6e037202-6438-4b22-90bd-fff653cafda2" xlink:to="loc_us-gaap_SaleOfStockNumberOfSharesIssuedInTransaction_83ef8aaa-891b-41d1-a622-244ef60d9d5e" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SaleOfStockPricePerShare_6afeb39e-e515-44af-b88a-667d29e304ed" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_SaleOfStockPricePerShare"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SubsidiarySaleOfStockLineItems_6e037202-6438-4b22-90bd-fff653cafda2" xlink:to="loc_us-gaap_SaleOfStockPricePerShare_6afeb39e-e515-44af-b88a-667d29e304ed" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_SaleOfStockUnderwriterOptionPeriod_0f32c35b-f582-496f-9443-792d2bf19e9a" xlink:href="espr-20250630.xsd#espr_SaleOfStockUnderwriterOptionPeriod"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SubsidiarySaleOfStockLineItems_6e037202-6438-4b22-90bd-fff653cafda2" xlink:to="loc_espr_SaleOfStockUnderwriterOptionPeriod_0f32c35b-f582-496f-9443-792d2bf19e9a" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SaleOfStockConsiderationReceivedOnTransaction_4e497ca1-b83c-4432-a3fc-f2d7c4c010a3" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_SaleOfStockConsiderationReceivedOnTransaction"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SubsidiarySaleOfStockLineItems_6e037202-6438-4b22-90bd-fff653cafda2" xlink:to="loc_us-gaap_SaleOfStockConsiderationReceivedOnTransaction_4e497ca1-b83c-4432-a3fc-f2d7c4c010a3" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PaymentsForCommissions_6e4dce44-ac6a-40e6-aeff-20920d75dfbc" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_PaymentsForCommissions"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SubsidiarySaleOfStockLineItems_6e037202-6438-4b22-90bd-fff653cafda2" xlink:to="loc_us-gaap_PaymentsForCommissions_6e4dce44-ac6a-40e6-aeff-20920d75dfbc" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_SaleOfStockAuthorizedAmount_f655d17c-c52c-43eb-aca0-332e10734795" xlink:href="espr-20250630.xsd#espr_SaleOfStockAuthorizedAmount"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SubsidiarySaleOfStockLineItems_6e037202-6438-4b22-90bd-fff653cafda2" xlink:to="loc_espr_SaleOfStockAuthorizedAmount_f655d17c-c52c-43eb-aca0-332e10734795" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PaymentsOfStockIssuanceCosts_7e1c816b-ffd0-4c7b-bd57-ad607aa2e164" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_PaymentsOfStockIssuanceCosts"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SubsidiarySaleOfStockLineItems_6e037202-6438-4b22-90bd-fff653cafda2" xlink:to="loc_us-gaap_PaymentsOfStockIssuanceCosts_7e1c816b-ffd0-4c7b-bd57-ad607aa2e164" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ClassOfWarrantOrRightOutstanding_d2f6a5e4-8eb9-4294-bc09-9b34ddbf1e37" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ClassOfWarrantOrRightOutstanding"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SubsidiarySaleOfStockLineItems_6e037202-6438-4b22-90bd-fff653cafda2" xlink:to="loc_us-gaap_ClassOfWarrantOrRightOutstanding_d2f6a5e4-8eb9-4294-bc09-9b34ddbf1e37" xlink:type="arc" order="7"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ClassOfWarrantOrRightExercisePriceOfWarrantsOrRights1_6fc08991-7801-426d-98c1-c19906d8106b" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ClassOfWarrantOrRightExercisePriceOfWarrantsOrRights1"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SubsidiarySaleOfStockLineItems_6e037202-6438-4b22-90bd-fff653cafda2" xlink:to="loc_us-gaap_ClassOfWarrantOrRightExercisePriceOfWarrantsOrRights1_6fc08991-7801-426d-98c1-c19906d8106b" xlink:type="arc" order="8"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AdjustmentsToAdditionalPaidInCapitalWarrantIssued_c587642a-a72c-4e8c-8fbc-f8779f0fa0d8" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_AdjustmentsToAdditionalPaidInCapitalWarrantIssued"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SubsidiarySaleOfStockLineItems_6e037202-6438-4b22-90bd-fff653cafda2" xlink:to="loc_us-gaap_AdjustmentsToAdditionalPaidInCapitalWarrantIssued_c587642a-a72c-4e8c-8fbc-f8779f0fa0d8" xlink:type="arc" order="9"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_ClassOfWarrantOrRightExpired_ede1eddc-53ba-45e9-99b4-88855252b9ba" xlink:href="espr-20250630.xsd#espr_ClassOfWarrantOrRightExpired"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SubsidiarySaleOfStockLineItems_6e037202-6438-4b22-90bd-fff653cafda2" xlink:to="loc_espr_ClassOfWarrantOrRightExpired_ede1eddc-53ba-45e9-99b4-88855252b9ba" xlink:type="arc" order="10"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ClassOfWarrantOrRightNumberOfSecuritiesCalledByWarrantsOrRights_9f0f17b8-0330-4045-8702-94247515b642" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ClassOfWarrantOrRightNumberOfSecuritiesCalledByWarrantsOrRights"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SubsidiarySaleOfStockLineItems_6e037202-6438-4b22-90bd-fff653cafda2" xlink:to="loc_us-gaap_ClassOfWarrantOrRightNumberOfSecuritiesCalledByWarrantsOrRights_9f0f17b8-0330-4045-8702-94247515b642" xlink:type="arc" order="11"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CommonStockSharesIssued_3e1c5ffd-4f3e-47ec-a199-a45e9dd34969" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_CommonStockSharesIssued"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SubsidiarySaleOfStockLineItems_6e037202-6438-4b22-90bd-fff653cafda2" xlink:to="loc_us-gaap_CommonStockSharesIssued_3e1c5ffd-4f3e-47ec-a199-a45e9dd34969" xlink:type="arc" order="12"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_CommonStockPurchasableUnderPrefundedWarrants_24e0de68-135f-4293-8ed8-92c725d31ee5" xlink:href="espr-20250630.xsd#espr_CommonStockPurchasableUnderPrefundedWarrants"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SubsidiarySaleOfStockLineItems_6e037202-6438-4b22-90bd-fff653cafda2" xlink:to="loc_espr_CommonStockPurchasableUnderPrefundedWarrants_24e0de68-135f-4293-8ed8-92c725d31ee5" xlink:type="arc" order="13"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_CommonStockPurchasableUnderWarrants_94737c91-5f79-46a4-b35b-b48d693b8bb9" xlink:href="espr-20250630.xsd#espr_CommonStockPurchasableUnderWarrants"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SubsidiarySaleOfStockLineItems_6e037202-6438-4b22-90bd-fff653cafda2" xlink:to="loc_espr_CommonStockPurchasableUnderWarrants_94737c91-5f79-46a4-b35b-b48d693b8bb9" xlink:type="arc" order="14"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_ClassOfWarrantOrRightPurchasePriceOfWarrantsOrRights_ea199c54-4db1-42b3-b1cd-cfd73612e93d" xlink:href="espr-20250630.xsd#espr_ClassOfWarrantOrRightPurchasePriceOfWarrantsOrRights"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SubsidiarySaleOfStockLineItems_6e037202-6438-4b22-90bd-fff653cafda2" xlink:to="loc_espr_ClassOfWarrantOrRightPurchasePriceOfWarrantsOrRights_ea199c54-4db1-42b3-b1cd-cfd73612e93d" xlink:type="arc" order="15"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CommonStockParOrStatedValuePerShare_04c803ea-6263-4525-9c09-1ba231b341a8" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_CommonStockParOrStatedValuePerShare"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SubsidiarySaleOfStockLineItems_6e037202-6438-4b22-90bd-fff653cafda2" xlink:to="loc_us-gaap_CommonStockParOrStatedValuePerShare_04c803ea-6263-4525-9c09-1ba231b341a8" xlink:type="arc" order="16"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_WarrantsAndRightsOutstandingTerm_2e2e7008-f149-4e8a-a760-cec0912aa9c6" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_WarrantsAndRightsOutstandingTerm"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SubsidiarySaleOfStockLineItems_6e037202-6438-4b22-90bd-fff653cafda2" xlink:to="loc_us-gaap_WarrantsAndRightsOutstandingTerm_2e2e7008-f149-4e8a-a760-cec0912aa9c6" xlink:type="arc" order="17"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_ClassOfWarrantOrRightExercisePriceOfWarrantsOrRightsAdditionalConsideration_5f4daa79-bcd2-4f23-be50-5f43bfce784f" xlink:href="espr-20250630.xsd#espr_ClassOfWarrantOrRightExercisePriceOfWarrantsOrRightsAdditionalConsideration"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SubsidiarySaleOfStockLineItems_6e037202-6438-4b22-90bd-fff653cafda2" xlink:to="loc_espr_ClassOfWarrantOrRightExercisePriceOfWarrantsOrRightsAdditionalConsideration_5f4daa79-bcd2-4f23-be50-5f43bfce784f" xlink:type="arc" order="18"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AdjustmentsToAdditionalPaidInCapitalStockIssuedIssuanceCosts_aa15af0a-a2db-4cf5-a54c-423beccd1a50" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_AdjustmentsToAdditionalPaidInCapitalStockIssuedIssuanceCosts"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SubsidiarySaleOfStockLineItems_6e037202-6438-4b22-90bd-fff653cafda2" xlink:to="loc_us-gaap_AdjustmentsToAdditionalPaidInCapitalStockIssuedIssuanceCosts_aa15af0a-a2db-4cf5-a54c-423beccd1a50" xlink:type="arc" order="19"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ProceedsFromIssuanceOfCommonStock_4e82e776-9842-4b0d-a525-68b798c49934" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ProceedsFromIssuanceOfCommonStock"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SubsidiarySaleOfStockLineItems_6e037202-6438-4b22-90bd-fff653cafda2" xlink:to="loc_us-gaap_ProceedsFromIssuanceOfCommonStock_4e82e776-9842-4b0d-a525-68b798c49934" xlink:type="arc" order="20"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PaymentsForRepurchaseOfPrivatePlacement_40e77429-54f6-478c-9ac0-ccc6149314fb" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_PaymentsForRepurchaseOfPrivatePlacement"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SubsidiarySaleOfStockLineItems_6e037202-6438-4b22-90bd-fff653cafda2" xlink:to="loc_us-gaap_PaymentsForRepurchaseOfPrivatePlacement_40e77429-54f6-478c-9ac0-ccc6149314fb" xlink:type="arc" order="21"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ProceedsFromDebtNetOfIssuanceCosts_11f519cc-6ad9-4e1e-a4cb-5aa98f2e9405" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ProceedsFromDebtNetOfIssuanceCosts"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SubsidiarySaleOfStockLineItems_6e037202-6438-4b22-90bd-fff653cafda2" xlink:to="loc_us-gaap_ProceedsFromDebtNetOfIssuanceCosts_11f519cc-6ad9-4e1e-a4cb-5aa98f2e9405" xlink:type="arc" order="22"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_ClassOfWarrantOrRightExercised_dbf22aa1-9da7-4e25-8ae7-1384b4a6c2fd" xlink:href="espr-20250630.xsd#espr_ClassOfWarrantOrRightExercised"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SubsidiarySaleOfStockLineItems_6e037202-6438-4b22-90bd-fff653cafda2" xlink:to="loc_espr_ClassOfWarrantOrRightExercised_dbf22aa1-9da7-4e25-8ae7-1384b4a6c2fd" xlink:type="arc" order="23"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.esperion.com/role/StockholdersDeficitSummaryofWarrantsandPrefundedWarrantsOutstandingDetails" xlink:type="simple" xlink:href="espr-20250630.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_9444100c-b289-42a7-9ac6-446a2e2e3bac" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_SubsidiarySaleOfStockLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SubsidiaryOrEquityMethodInvesteeSaleOfStockBySubsidiaryOrEquityInvesteeTable_cc20ca99-876e-4feb-87f5-79334474b779" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_SubsidiaryOrEquityMethodInvesteeSaleOfStockBySubsidiaryOrEquityInvesteeTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_SubsidiarySaleOfStockLineItems_9444100c-b289-42a7-9ac6-446a2e2e3bac" xlink:to="loc_us-gaap_SubsidiaryOrEquityMethodInvesteeSaleOfStockBySubsidiaryOrEquityInvesteeTable_cc20ca99-876e-4feb-87f5-79334474b779" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_TypeOfArrangementAxis_b3c6a2d4-bfd5-4e7d-9e13-2005dd0d8ddf" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_TypeOfArrangementAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_SubsidiaryOrEquityMethodInvesteeSaleOfStockBySubsidiaryOrEquityInvesteeTable_cc20ca99-876e-4feb-87f5-79334474b779" xlink:to="loc_us-gaap_TypeOfArrangementAxis_b3c6a2d4-bfd5-4e7d-9e13-2005dd0d8ddf" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ArrangementsAndNonarrangementTransactionsMember_b3c6a2d4-bfd5-4e7d-9e13-2005dd0d8ddf_default" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ArrangementsAndNonarrangementTransactionsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_TypeOfArrangementAxis_b3c6a2d4-bfd5-4e7d-9e13-2005dd0d8ddf" xlink:to="loc_us-gaap_ArrangementsAndNonarrangementTransactionsMember_b3c6a2d4-bfd5-4e7d-9e13-2005dd0d8ddf_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ArrangementsAndNonarrangementTransactionsMember_b206cf78-678d-491c-8c52-6302fa910611" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ArrangementsAndNonarrangementTransactionsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_TypeOfArrangementAxis_b3c6a2d4-bfd5-4e7d-9e13-2005dd0d8ddf" xlink:to="loc_us-gaap_ArrangementsAndNonarrangementTransactionsMember_b206cf78-678d-491c-8c52-6302fa910611" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_WarrantAmendmentAgreementsMember_22d3f0c4-1a31-4287-aff3-91b448f6fc16" xlink:href="espr-20250630.xsd#espr_WarrantAmendmentAgreementsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ArrangementsAndNonarrangementTransactionsMember_b206cf78-678d-491c-8c52-6302fa910611" xlink:to="loc_espr_WarrantAmendmentAgreementsMember_22d3f0c4-1a31-4287-aff3-91b448f6fc16" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_SecuritiesPurchaseAgreementMember_2a7200b2-37d6-4e47-8804-540391d93cf6" xlink:href="espr-20250630.xsd#espr_SecuritiesPurchaseAgreementMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ArrangementsAndNonarrangementTransactionsMember_b206cf78-678d-491c-8c52-6302fa910611" xlink:to="loc_espr_SecuritiesPurchaseAgreementMember_2a7200b2-37d6-4e47-8804-540391d93cf6" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ClassOfWarrantOrRightOutstanding_182a54d4-68e1-486e-91c8-65059b3022e1" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ClassOfWarrantOrRightOutstanding"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SubsidiarySaleOfStockLineItems_9444100c-b289-42a7-9ac6-446a2e2e3bac" xlink:to="loc_us-gaap_ClassOfWarrantOrRightOutstanding_182a54d4-68e1-486e-91c8-65059b3022e1" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ClassOfWarrantOrRightExercisePriceOfWarrantsOrRights1_ce3325aa-e6be-4e81-bfcf-eb3c071da8a8" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ClassOfWarrantOrRightExercisePriceOfWarrantsOrRights1"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SubsidiarySaleOfStockLineItems_9444100c-b289-42a7-9ac6-446a2e2e3bac" xlink:to="loc_us-gaap_ClassOfWarrantOrRightExercisePriceOfWarrantsOrRights1_ce3325aa-e6be-4e81-bfcf-eb3c071da8a8" xlink:type="arc" order="1"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.esperion.com/role/NetLossPerCommonShareDetails" xlink:type="simple" xlink:href="espr-20250630.xsd#NetLossPerCommonShareDetails"/>
  <link:definitionLink xlink:role="http://www.esperion.com/role/NetLossPerCommonShareDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareLineItems_cc217bbd-b2dd-44ce-9629-cf90e330e696" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfAntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareTable_e10618a5-2298-498a-8a03-103092eca167" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ScheduleOfAntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareLineItems_cc217bbd-b2dd-44ce-9629-cf90e330e696" xlink:to="loc_us-gaap_ScheduleOfAntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareTable_e10618a5-2298-498a-8a03-103092eca167" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareByAntidilutiveSecuritiesAxis_0d421eb2-2447-4cbb-9812-663924d69e9a" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareByAntidilutiveSecuritiesAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfAntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareTable_e10618a5-2298-498a-8a03-103092eca167" xlink:to="loc_us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareByAntidilutiveSecuritiesAxis_0d421eb2-2447-4cbb-9812-663924d69e9a" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AntidilutiveSecuritiesNameDomain_0d421eb2-2447-4cbb-9812-663924d69e9a_default" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_AntidilutiveSecuritiesNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareByAntidilutiveSecuritiesAxis_0d421eb2-2447-4cbb-9812-663924d69e9a" xlink:to="loc_us-gaap_AntidilutiveSecuritiesNameDomain_0d421eb2-2447-4cbb-9812-663924d69e9a_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AntidilutiveSecuritiesNameDomain_0063edd5-1377-420d-b24c-be0d794d9984" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_AntidilutiveSecuritiesNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareByAntidilutiveSecuritiesAxis_0d421eb2-2447-4cbb-9812-663924d69e9a" xlink:to="loc_us-gaap_AntidilutiveSecuritiesNameDomain_0063edd5-1377-420d-b24c-be0d794d9984" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EmployeeStockOptionMember_ecbf7d4c-998a-450d-a289-1f4162bd5c33" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_EmployeeStockOptionMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AntidilutiveSecuritiesNameDomain_0063edd5-1377-420d-b24c-be0d794d9984" xlink:to="loc_us-gaap_EmployeeStockOptionMember_ecbf7d4c-998a-450d-a289-1f4162bd5c33" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_ShareBasedPaymentArrangementOptionPerformanceBasedMember_9ef0b92d-735b-46ed-a1b0-b94c664b37ab" xlink:href="espr-20250630.xsd#espr_ShareBasedPaymentArrangementOptionPerformanceBasedMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AntidilutiveSecuritiesNameDomain_0063edd5-1377-420d-b24c-be0d794d9984" xlink:to="loc_espr_ShareBasedPaymentArrangementOptionPerformanceBasedMember_9ef0b92d-735b-46ed-a1b0-b94c664b37ab" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_espr_UnvestedRestrictedStockAndRestrictedStockUnitsMember_e93a9ee7-d2c2-4755-b4ac-0de9cfe84c0f" xlink:href="espr-20250630.xsd#espr_UnvestedRestrictedStockAndRestrictedStockUnitsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AntidilutiveSecuritiesNameDomain_0063edd5-1377-420d-b24c-be0d794d9984" xlink:to="loc_espr_UnvestedRestrictedStockAndRestrictedStockUnitsMember_e93a9ee7-d2c2-4755-b4ac-0de9cfe84c0f" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EmployeeStockMember_b9044cb9-41f3-4f09-9273-dbab875d6463" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_EmployeeStockMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AntidilutiveSecuritiesNameDomain_0063edd5-1377-420d-b24c-be0d794d9984" xlink:to="loc_us-gaap_EmployeeStockMember_b9044cb9-41f3-4f09-9273-dbab875d6463" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ConvertibleDebtSecuritiesMember_817604dd-3b03-4763-8b2a-188f01c9b25f" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ConvertibleDebtSecuritiesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AntidilutiveSecuritiesNameDomain_0063edd5-1377-420d-b24c-be0d794d9984" xlink:to="loc_us-gaap_ConvertibleDebtSecuritiesMember_817604dd-3b03-4763-8b2a-188f01c9b25f" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_WarrantMember_4d2d8bb7-0880-4a81-a766-2a3de298aa74" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_WarrantMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AntidilutiveSecuritiesNameDomain_0063edd5-1377-420d-b24c-be0d794d9984" xlink:to="loc_us-gaap_WarrantMember_4d2d8bb7-0880-4a81-a766-2a3de298aa74" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AwardTypeAxis_3f5bf394-eb16-408e-b398-55af94449e3d" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_AwardTypeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfAntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareTable_e10618a5-2298-498a-8a03-103092eca167" xlink:to="loc_us-gaap_AwardTypeAxis_3f5bf394-eb16-408e-b398-55af94449e3d" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_3f5bf394-eb16-408e-b398-55af94449e3d_default" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_AwardTypeAxis_3f5bf394-eb16-408e-b398-55af94449e3d" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_3f5bf394-eb16-408e-b398-55af94449e3d_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_5d1d108d-e6c3-4976-95c0-4085159f2a9e" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_AwardTypeAxis_3f5bf394-eb16-408e-b398-55af94449e3d" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_5d1d108d-e6c3-4976-95c0-4085159f2a9e" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EmployeeStockOptionMember_86b0e684-e056-44cf-9b0c-684d638a5065" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_EmployeeStockOptionMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_5d1d108d-e6c3-4976-95c0-4085159f2a9e" xlink:to="loc_us-gaap_EmployeeStockOptionMember_86b0e684-e056-44cf-9b0c-684d638a5065" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareAmount_4fe30560-8964-4b9c-8054-4c04d6b7aa8d" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareAmount"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareLineItems_cc217bbd-b2dd-44ce-9629-cf90e330e696" xlink:to="loc_us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareAmount_4fe30560-8964-4b9c-8054-4c04d6b7aa8d" xlink:type="arc" order="0"/>
  </link:definitionLink>
</link:linkbase>
