Several medications have individually been shown to reduce mortality in patients with acute coronary syndromes (ACS), but data on long-term outcomes related to the use of combinations of these medications are limited. For 2,684 consecutive patients admitted with ACS from January 1999 and January 2007, a composite score was calculated correlating with the use upon discharge of indicated evidence-based medications (EBMs): aspirin, β blockers, angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, and lipid-lowering agents. Multivariate models were used to examine the impact of EBM score on 2-year events with adjustment for components of the Global Registry of Acute Coronary Events (GRACE) risk score, thienopyridine use, and year of discharge. Women were older, had more co-morbidities, and were less likely to receive all 4 EBMs (53% vs 64%, p < 0.0001) than men. Patients who received all 4 indicated EBMs had a significant 2-year survival benefit compared to patients who received ≤1 EBM (odds ratio 0.25, 95% confidence interval 0.15 to 0.41), which was observed when men and women were examined separately (for men, odds ratio 0.22, 95% confidence interval 0.11 to 0.44; for women, odds ratio 0.3, 95% confidence interval 0.15 to 0.63). A modest benefit, in terms of cardiovascular disease events (myocardial infarction, rehospitalization, stroke, and death), was observed only for men who received all 4 EBMs. In conclusion, a combination of cardiac medications at the time of ACS discharge is strongly associated with 2-year survival in men and women, suggesting that discharge is an important time to prescribe secondary preventative medications. © 2012 Elsevier Inc.