This study examines the relationship between body-mass index (BMI) and all-cause mortality in a large, diverse cohort of 1.46 million white adults. The median BMI was 26.2, and the median follow-up period was 10 years. The results show a J-shaped relationship between BMI and mortality, with the lowest mortality observed in the BMI range of 20.0 to 24.9. Overweight and obesity (and possibly underweight) were associated with increased all-cause mortality, particularly among healthy participants who never smoked. The hazard ratios for higher and lower BMIs increased with age, and longer follow-up attenuated the associations with lower BMI levels. The findings suggest that for non-Hispanic whites, optimal BMI is within the range of 20.0 to 24.9, and that both overweight and obesity are associated with increased mortality.This study examines the relationship between body-mass index (BMI) and all-cause mortality in a large, diverse cohort of 1.46 million white adults. The median BMI was 26.2, and the median follow-up period was 10 years. The results show a J-shaped relationship between BMI and mortality, with the lowest mortality observed in the BMI range of 20.0 to 24.9. Overweight and obesity (and possibly underweight) were associated with increased all-cause mortality, particularly among healthy participants who never smoked. The hazard ratios for higher and lower BMIs increased with age, and longer follow-up attenuated the associations with lower BMI levels. The findings suggest that for non-Hispanic whites, optimal BMI is within the range of 20.0 to 24.9, and that both overweight and obesity are associated with increased mortality.