Aims To determine independent associations of diabetes mellitus with outcomes in a propensity-matched cohort of patients with acute myocardial infarction (AMI) and systolic heart failure (HF). Methods and resultsIn the Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study (EPHESUS) trial, hospitalized AMI patients complicated by left ventricular ejection fraction ≤40 and symptoms of HF receiving standard therapy were randomized 314 days post-AMI to receive eplerenone 2550 mg/day (n 3319) or placebo (n 3313). Of the 6632 patients, 2142 (32) had a history of diabetes, who were older and sicker. Using propensity scores for diabetes, we assembled a cohort of 1119 pairs of patients with and without diabetes who were balanced on 64 baseline characteristics. Incident fatal or nonfatal recurrent AMI occurred in 136 (12) and 87 (8) of matched patients with and without diabetes, respectively, during 2.5 years of follow-up [hazard ratio (HR) when diabetes was compared with no-diabetes, 1.61; 95 confidence interval (CI), 1.232.10; P 0.001]. Diabetes was associated with nonfatal AMI (HR, 1.68; 95 CI, 1.232.31; P 0.001) but not with fatal AMI (HR, 1.42; 95 CI, 0.882.28; P 0.146). Hazard ratios (95 CIs) for the association of diabetes with all-cause mortality, cardiovascular mortality, all-cause hospitalization, and cardiovascular hospitalization were 1.12 (0.931.37; P 0.224), 1.11 (0.901.37; P 0.318), 1.13 (1.001.27; P 0.054), and 1.20 (1.011.44; P 0.042), respectively. Conclusion In post-AMI patients with systolic HF, diabetes mellitus is a significant independent risk factor for recurrent short-term nonfatal AMI, but had no association with fatal AMI. © 2011 The Author.