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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).In 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 3–14 days post-AMI to receive eplerenone 25–50 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), 1.23–2.10; P = 0.001]. Diabetes was associated with nonfatal AMI (HR, 1.68; 95% CI, 1.23–2.31; P = 0.001) but not with fatal AMI (HR, 1.42; 95% CI, 0.88–2.28; 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 (0.93–1.37; P = 0.224), 1.11 (0.90–1.37; P = 0.318), 1.13 (1.00–1.27; P = 0.054), and 1.20 (1.01–1.44; P = 0.042), respectively.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.