Body mass index (BMI) has been strongly related to overall mortality, but the consistency of this association across diverse ethnic groups and the effects of early adult BMI versus BMI in later adulthood have not been adequately studied. A prospective analysis was performed using data from 183,211 adults aged 45-75 who enrolled the population-based Multiethnic Cohort Study by completing a questionnaire that included self-reported weight and height information in 1993-1996. Participants were African Americans, Native Hawaiians, Japanese Americans, Latinos, and whites living in Hawaii and California. During an average 12.5 years of follow-up, 35,664 deaths were identified. To control for confounding caused by conditions that lead to weight loss and mortality, we excluded participants with a history of cancer or heart disease, who ever smoked, and who died within the first 3 years of follow-up. An increased risk of mortality was observed in participants with a BMI ≥ 27.5 in both men and women compared with the reference category of BMI 23.0-24.9; a BMI ≥ 35.0 carried a greater risk of mortality in men than in women. Although the findings were generally similar across ethnic groups, the association of higher BMI with mortality in Latino men appeared to be weaker than in the other groups. A BMI of 25.0-34.9 at age 21 showed a stronger positive association, with no further increase in risk for a BMI ≥ 35.0, than did BMI in later adulthood. These results indicate that the association of BMI with mortality is generally consistent across sex and ethnic groups, with some variation in the strength of the effect. Most notably, the effect of overweight in young adulthood appears to be much stronger than that of overweight in later adulthood on mortality in later life. This emphasizes the importance of weight management in childhood and adolescence.