BACKGROUND The role of weight training in the primary prevention of type 2 diabetes mellitus (T2DM) is largely unknown. METHODS To examine the association of weight training with risk of T2DM in US men and to assess the influence of combining weight training and aerobic exercise, we performed a prospective cohort study of 32 002 men from the Health Professionals Follow-up Study observed from 1990 to 2008. Weekly time spent on weight training and aerobic exercise (including brisk walking, jogging, running, bicycling, swimming, tennis, squash, and calisthenics/rowing) was obtained from questionnaires at baseline and biennially during follow-up. RESULTS During 508 332 person-years of follow-up (18 years), we documented 2278 new cases of T2DM. In multivariable-adjusted models, we observed a dose-response relationship between an increasing amount of time spent on weight training or aerobic exercise and lower risk of T2DM (P < .001 for trend). Engaging in weight training or aerobic exercise for at least 150 minutes per week was independently associated with a lower risk of T2DM of 34% (95% CI, 7%-54%) and 52% (95% CI, 45%-58%), respectively. Men who engaged in aerobic exercise and weight training for at least 150 minutes per week had the greatest reduction in T2DM risk (59%; 95% CI, 39%-73%). CONCLUSIONS Weight training was associated with a significantly lower risk of T2DM, independent of aerobic exercise. Combined weight training and aerobic exercise conferred a greater benefit.