Background: Clinical guidelines recommend beta-blockers, angiotensin-converting enzyme inhibitors/angiotensin-receptor blockers, and statins for the secondary prevention of acute myocardial infarction (AMI). It is not clear whether variation in real-world practice reflects poor quality-of-care or a balance of outcome tradeoffs across patients. Methods: The study cohort included Medicare fee-for-service beneficiaries hospitalized 2007–2008 for AMI. Treatment within 30-days post-discharge was grouped into one of eight possible combinations for the three drug classes. Outcomes included one-year overall survival, one-year cardiovascular-event-free survival, and 90-day adverse events. Treatment effects were estimated using an Instrumental Variables (IV) approach with instruments based on measures of local-area practice style. Pre-specified data elements were abstracted from hospital medical records for a stratified, random sample to create “unmeasured confounders” (per claims data) and assess model assumptions. Results: Each drug combination was observed in the final sample (N = 124,695), with 35.7% having all three, and 13.5% having none. Higher rates of guideline-recommended treatment were associated with both better survival and more adverse events. Unmeasured confounders were not associated with instrumental variable values. Conclusions: The results from this study suggest that providers consider both treatment benefits and harms in patients with AMIs. The investigation of estimator assumptions support the validity of the estimates. View Full-Text ►▼ Show Figures This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.