Obesity has been identified as a risk factor for cardiovascular disease and heart failure. However, data regarding the relation of body mass index (BMI) to outcome in patients with established heart failure are conflicting. We examined the risk of all-cause mortality and sudden cardiac death (SCD) in 1,231 patients after myocardial infarction with left ventricular dysfunction enrolled the Multicenter Automatic Defibrillator Implantation Trial-II (MADIT-II). Interaction-term analysis was used to assess the benefit of the implantable cardioverter-defibrillator (ICD) in upper (obese ≥30 kg/m2, n = 361) and lower (nonobese <30 kg/m2, n = 870) BMI categories. Mean BMI in the study population was 27.9 ± 5.1 kg/m2. In multivariate analysis, decreased BMI was shown to be independently associated with an increase in the risk of all-cause mortality (23% risk increase per 5-U BMI decreased, p = 0.009) and SCD (41% risk increase per 5-U BMI decrease, p = 0.01). Consistently, patients with BMI <30 kg/m2 exhibited 46% (p = 0.03) and 76% (p = 0.04) increases in risk of all-cause mortality and SCD, respectively, compared to patients who had higher BMI values. The benefit of the ICD was pronounced in higher-risk patients with BMI <30 kg/m2 (hazard ratio 0.68, p = 0.017) and maintained in the lower-risk subgroup of patients with BMI ≥30 kg/m2 (hazard ratio 0.73, p = 0.32; p = 0.86 for ICD-by-BMI interaction). In conclusion, our findings suggest an independent inverse association between BMI values and risk of all-cause mortality and SCD in patients after myocardial infarction with left ventricular dysfunction enrolled in the MADIT-II trial.