International guidelines recommend long-term use of evidence-based treatment (EBT) combining beta-blockers, aspirin/clopidogrel, statins and either angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (ACEIs/ARBs) after a myocardial infarction (MI), to reduce cardiac morbidity and mortality. To evaluate medication adherence after hospital admission for MI and the relationship with mortality and readmission for acute coronary syndrome. Observational, 30-month follow-up of patients admitted for acute MI in France in the first half of 2006 and still alive 6 months later. Data from the national hospital discharge database and the outpatient medications reimbursement database were linked for all patients covered by the general health insurance scheme (70% of the French population). A patient was considered as adherent when the proportion of days covered by a filled prescription was greater than 80%. The proportion of nonadherent patients was 32.0% for beta-blockers, 24.0% for statins, 22.7% for ACEIs/ARBs, 18.3% for aspirin/clopidogrel and 50.0% for combined EBT. Adherence to EBT was decreased significantly by age greater than 74 years, comorbidities and full healthcare coverage for low earners. Prior EBT use and stent implantation, before or during index hospitalization, increased adherence. After adjustment for patient characteristics and management, prior use of each class decreased mortality. Nonadherence to EBT after MI increased mortality and readmission (hazard ratio=1.43, P<0.0001). After MI, nonadherence to EBT is associated with a marked increase in all-cause mortality and readmission for acute coronary syndrome. Cost-effective strategies for adherence improvement should be developed among patient groups with poor adherence.