Aims To determine the association between obesity and outcomes in post-acute myocardial infarction (AMI) patients with systolic heart failure (HF). Methods and results Of the 6632 Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study (EPHESUS) participants, 6611 had data on baseline body mass index (BMI) and 6561 had BMI ≥ 18.5 kg/m2. Of these, 1573 were obese (BMI ≥ 30 kg/m2) and 4988 were non-obese (BMI 18.5-29.9 kg/m2). Propensity scores for obesity, estimated for each patient, were used to assemble a cohort of 1519 pairs of obese and non-obese patients who were balanced on 65 baseline characteristics. All-cause mortality occurred in 13.7 and 13.8 of matched obese and non-obese patients, respectively, during 16 months of median follow-up [matched hazard ratio (HR) for obesity 0.98; 95 confidence interval (CI) 0.79-1.21; P = 0.831]. Before matching, the obese group was younger (mean age, 62 vs. 64 years; P < 0.0001) and had more women (37 vs. 26; P < 0.0001). The paradoxical pre-match association between obesity and reduced mortality (unadjusted HR 0.82; 95 CI 0.70-0.95; P = 0.008) disappeared when adjusted for age alone (age-adjusted HR 0.91; 95 CI 0.78-1.06; P = 0.206) but not for gender alone (gender-adjusted HR 0.79; 95 CI 0.68-0.92; P = 0.003). Obesity had no association with mortality in 1573 pairs of age-matched obese and non-obese patients (age-adjusted HR 0.94; 95 CI 0.77-1.13; P = 0.484). Conclusion In post-AMI patients with systolic HF, obesity provides no independent intrinsic survival benefit. The paradoxical unadjusted survival associated with obesity is largely explained by the younger age of obese patients. © 2010 The Author.