This prospective cohort study of 20,757 men investigated the independent and joint associations between vigorous activity and body mass index (BMI) on diabetes risk in men. When BMI and physical activity were analyzed jointly, results showed that diabetes risk was most strongly related to increasing BMI and comparatively less influenced by activity. Even among active participants, increasing BMI was strongly associated with increased diabetes risk. The risk from elevated BMI was modestly but significantly reduced by weekly physical activity in normal weight and overweight men. The risk attenuation among obese men was observed only when the frequency of vigorous activity reached ≥5 times weekly. These data underscore the important association between obesity and diabetes.