Although guideline-recommended therapies reduce major adverse cardiovascular events (MACE) in patients after myocardial infarction (MI) or those with atherosclerotic disease (ATH), adherence is poor.The goal of this study was to determine the association between medication adherence levels and long-term MACE in these patients.We queried the claims database of a large health insurer for patients hospitalized for MI or with ATH. The primary outcome measure was a composite of all-cause death, MI, stroke, or coronary revascularization. Using proportion of days covered for statins and angiotensin-converting enzyme inhibitors, patients were stratified as fully adherent (≥80%), partially adherent (≥40% to ≤79%), or nonadherent (80% adherence in the post-MI population; at least a 40% level of long-term adherence needs to be maintained to continue to accrue benefit. Novel approaches to improve adherence may significantly reduce cardiovascular events.