Background: Little is known about the effect of nonadherence among patients with coronary artery disease (CAD) on a broad spectrum of outcomes including cardiovascular mortality, cardiovascular hospitalizations, and revascularization procedures. Methods: This was a retrospective cohort study of 15 767 patients with CAD. Medication adherence was calculated as proportion of days covered for filled prescriptions of β-blockers, angiotensin-converting enzyme (ACE) inhibitors, and statin medications. Multivariable Cox regression assessed the association between medication nonadherence as a time-varying covariate and a broad range of outcomes, adjusting for demographics and clinical characteristics. Median follow-up was 4.1 years. Results: Rates of medication nonadherence were 28.8% for β-blockers, 21.6% for ACE inhibitors, and 26.0% for statins. In unadjusted analysis, nonadherence to each class of medication was associated with higher all-cause and cardiovascular mortality. In multivariable analysis, nonadherence remained significantly associated with increased all-cause mortality risk for β-blockers (hazard ratio [HR] 1.50, 95% CI 1.33-1.71), ACE inhibitors (HR 1.74, 95% CI 1.52-1.98), and statins (HR 1.85, 95% CI 1.63-2.09). In addition, nonadherence remained significantly associated with higher risk of cardiovascular mortality for β-blockers (HR 1.53, 95% CI 1.16-2.01), ACE inhibitors (HR 1.66, 95% CI 1.26-2.20), and statins (HR 1.62, 95% CI 1.124-2.13). The findings of increased risk associated with nonadherence were consistent for cardiovascular hospitalization and revascularization procedures. Conclusions: Nonadherence to cardioprotective medications is common in clinical practice and associated with a broad range of adverse outcomes. These findings suggest that medication nonadherence should be a target for quality improvement interventions to maximize the outcomes of patients with CAD.