© 2017 American College of Cardiology Foundation Background Many patients report adverse reactions to, and may not tolerate, statin therapy. These patients may be at increased risk for coronary heart disease (CHD) events and mortality. Objectives This study evaluated the risk for recurrent myocardial infarction (MI), CHD events, and all-cause mortality in Medicare beneficiaries with statin intolerance and in those with high adherence to statin therapy. Methods We studied 105,329 Medicare beneficiaries who began a moderate- or high-intensity statin dosage after hospitalization for MI between 2007 and 2013. Statin intolerance was defined as down-titrating statins and initiating ezetimibe therapy, switching from statins to ezetimibe monotherapy, having International Classification of Diseases, 9th revision, diagnostic codes for rhabdomyolysis or an antihyperlipidemic adverse event, followed by statin down-titration or discontinuation, or switching between ≥3 types of statins within 1 year after initiation. High statin adherence over the year following hospital discharge was defined as proportion of days covered ≥80%. Recurrent MI, CHD events (recurrent MI or a coronary revascularization procedure), and mortality were identified from 1 year after hospital discharge through December 2014. Results Overall, 1,741 patients (1.65%) had statin intolerance, and 55,567 patients (52.8%) had high statin adherence. Over a median of 1.9 to 2.3 years of follow-up, there were 4,450 recurrent MIs, 6,250 CHD events, and 14,311 deaths. Compared to beneficiaries with high statin adherence, statin intolerance was associated with a 36% higher rate of recurrent MI (41.1 vs. 30.1 per 1,000 person-years, respectively), a 43% higher rate of CHD events (62.5 vs. 43.8 per 1,000 person-years, respectively), and a 15% lower rate of all-cause mortality (79.9 vs. 94.2 per 1,000 person-years, respectively). The multivariate-adjusted hazard ratios (HR) comparing beneficiaries with statin intolerance versus those with high statin adherence were 1.50 (95% confidence interval [CI]: 1.30 to 1.73) for recurrent MI, 1.51 (95% CI: 1.34 to 1.70) for CHD events, and 0.96 (95% CI: 0.87 to 1.06) for all-cause mortality. Conclusions Statin intolerance was associated with an increased risk for recurrent MI and CHD events but not all-cause mortality.