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Background: The relation between BMI, weight change and mortality among survivors of Myocardial Infarction (MI) remains controversial, with some studies reporting favorable survival outcomes among overweight and obese patients, as compared to those with normal weight. We aim to examine the relationship between BMI reported shortly before and after MI diagnosis in addition to weight change with all-cause and cardiovascular disease (CVD) mortality among MI survivors.Methods: Using the data from Nurses’ Health Study (NHS) and Health Professionals Follow up Study (HPFS) cohorts, we studied 4278 participants who were free of CVD and cancer before their MI. Weight change (in BMI units) was categorized as loss of (> 4, 2-4, <2-0 (reference)), or gain of (0.1-2, or >2) units. Multivariable Cox models were used to estimate hazard ratios and 95 % confidence interval for mortality across BMI/weight change categories.Results: During up to 36 (NHS) and 28 (HPFS) years of follow-up post-MI, there were 2071 all-cause and 835 CVD deaths. Overweight patients with BMI before or after MI of 25-27.49 kg/m2 had decreased mortality as compared to normal weight patients (22.5-24.9 kg/m2). All-cause mortality increased progressively with higher BMI. Obese patients (BMI≥30) had the highest risk of CVD mortality (HR=1.35; 95% CI, 1.06-1.73). Among MI patients who had never smoked (N=1484) or were younger than 65 years of age at the time of diagnosis (N=1873), no survival advantage was observed for overweight/obese patients. Compared to stable weight (a BMI reduction of 0-1.99 units) from before to after MI, a reduction of 2-4 or >4 BMI units was associated with increased mortality (HR=1.12; 95% CI, 0.96-1.29 and 1.42; 95% CI, 1.17-1.71 respectively, Figure).Conclusions: We observed a J-shaped association between BMI and mortality among all MI patients, but not among those who had never smoked or were younger than 65 years of age. Weight loss associated with acute MI, potentially related to disease severity, is an important predictor of higher mortality.