Background: Adherence to evidence-based medications after myocardial infarction is associated with improved outcomes. However, long-term data on factors affecting medication adherence after myocardial infarction are lacking. Methods: Olmsted County residents hospitalized with myocardial infarction from 1997-2006 were identified. Adherence to HMG-CoA reductase inhibitors (statins), beta blockers, angiotensin-converting enzyme inhibitors, and angiotensin II receptor blockers, were examined. Cox proportional hazard regression was used to determine the factors associated with medication adherence over time. Results: Among 292 subjects with incident myocardial infarction (63% men, mean age 65 years), patients were followed for an average of 52 ± 31 months. Adherence to guideline-recommended medications decreased over time, with 3-year medication continuation rates of 44%, 48%, and 43% for statins, beta-blockers, and angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers, respectively. Enrollment in a cardiac rehabilitation program was associated with an improved likelihood of continuing medications, with adjusted hazard ratio (95% confidence interval) for discontinuation of statins and beta-blockers among cardiac rehabilitation participants of 0.66 (0.45-0.92) and 0.70 (0.49-0.98), respectively. Smoking at the time of myocardial infarction was associated with a decreased likelihood of continuing medications, although results did not reach statistical significance. There were no observed associations between demographic characteristics, clinical characteristics of the myocardial infarction, and medication adherence. Conclusions: After myocardial infarction, a large proportion of patients discontinue use of medications over time. Enrollment in cardiac rehabilitation after myocardial infarction is associated with improved medication adherence. © 2009 Elsevier Inc. All rights reserved.