Background Although recent meta-analysis trials have shown that exercise training may improve survival after myocardial infarction, the mechanism of this beneficial effect is still unknown. The purpose of this study was to detect possible interactions between exercise training and predictors of prognosis after a first myocardial infarction. Methods and Results Patients with uneventful clinical courses after a first myocardial infarction were randomly assigned to a 4-week training period (125 patients, group 1) or to a control group (131 patients, group 2). Before randomization, all patients underwent a symptom-limited exercise test (28±2 days after myocardial infarction), 24-hour Holter monitoring, and coronary arteriography (31±3 days after the acute episode). After a mean follow-up period of 34.5 months, 18 patients had cardiac deaths (5 in group 1 and 13 in group 2). Multivariate analysis by Cox regression model showed that ejection fraction was the only independent prognostic indicator ( P =.03). Evidence existed of an interaction between ejection fraction and exercise training, showing an effect of physical training on survival that depended on the patient's ejection fraction. Among patients with ejection fractions <41%, the relative risk for an untrained patient was 8.63 times higher than for a trained patient ( P =.04), whereas for ejection fractions >40%, the estimated risks for trained and untrained patients were similar. Conclusions These data show that exercise training may prolong survival in post-myocardial infarction patients with depressed left ventricular function. A randomized trial in such patients seems warranted.