Few studies have delineated body mass index (BMI) trajectories that associate with premature mortality, which is defined as death occurring before age 75 years. We used generalized additive mixed model to identify BMI trajectories of individuals dying before or after age 75 years among 14,172 U.S. men. We used logistic regression to validate whether the BMI trajectory developed predicted mortality in an independent cohort of 7000 participants. Comparing to participants with age at death less than 75 years, the BMI among participants with age at death 75 years or more was lower throughout adulthood, and the mean BMI was 23.98, 24.63, 25.33, and 25.29 kg/m2 at age 40, 50, 60, and 70 years. In the validation cohort, participants following the BMI trajectory with age at death less than 75 years had higher risks of total mortality (odds ratio: 1.35; 95% confidence interval: 1.01-1.78) and cardiovascular disease mortality (1.92; 1.10-3.35) compared to participants following the trajectory with age at death 75 years or more. Participants whose BMI trajectories diverged the most from the trajectory with age at death 75 years or more had highest risks of total mortality (1.72; 1.23-2.40) and cardiovascular disease mortality (3.06; 1.49-6.30). Individual is suggested to maintain a normal BMI throughout adulthood to have greater longevity.