AIMS: To explore the influence of obesity on prognosis in high-risk patients with myocardial infarction (MI) or heart failure (HF). METHODS AND RESULTS: Individual data of 21 570 consecutively hospitalized patients from five Danish registries were pooled together. After a follow-up of 10.4 years, all-cause mortality using multivariate model and adjusted hazard ratios (HR) with 95% confidence intervals were calculated. Compared with normal weight [body mass index (BMI) 18.5-24.9 kg/m2], obesity class II (BMI >or= 35 kg/m2) was associated with increased risk of death in patients with MI but not HF [HR = 1.23 (1.06-1.44), P = 0.006 and HR = 1.13 (0.95-1.36), P = 0.95] (P-value for interaction = 0.004). Obesity class I (BMI 30-34.9 kg/m2) was not associated with increased risk of death in MI or HF [HR = 0.99 (0.92-1.08) and 1.00 (0.90-1.11), P > 0.1]. Pre-obesity (BMI 25-29.9 kg/m2) was associated with decreased death risk in MI but not HF [HR = 0.91 (0.87-0.96), P = 0.0006 and 1.04 (0.97-1.12), P = 0.34] (P-value for interaction = 0.007). Underweight (BMI < 18.5 kg/m2) patients were in increased death risk regardless of MI or HF [HR = 1.54 (1.35-1.75) and 1.37 (1.18-1.59), P < 0.001]. CONCLUSION: In patients with MI but not HF, the relationship between BMI and mortality is U-shaped with highest mortality in underweight and obese class II, but lowest in the other BMI classes.