To examine ethnic differences in risk of type 2 diabetes, taking dietary and lifestyle risk factors into account. A prospective (1980-2000) cohort (from The Nurses' Health Study) including 78,419 apparently healthy women (75,584 whites, 801 Asians, 613 Hispanics, and 1,421 blacks) was studied. Detailed dietary and lifestyle information for each participant was repeatedly collected every 4 years. During 1,294,799 person-years of follow-up, we documented 3,844 incident cases of diabetes. Compared with whites, the age-adjusted relative risks (RRs) were 1.43 (95% CI 1.08-1.90) for Asians, 1.76 (1.32-2.34) for Hispanics, and 2.18 (1.82-2.61) for blacks. After adjustment for BMI, the RRs changed to 2.26 (1.70-2.99) for Asians, 1.86 (1.40-2.47) for Hispanics, and 1.34 (1.12-1.61) for blacks. For each 5-unit increment in BMI, the multivariate RR of diabetes was 2.36 (1.83-3.04) for Asians, 2.21 (1.75-2.79) for Hispanics, 1.96 (1.93-2.00) for whites, and 1.55 (1.36-1.77) for blacks (P for interaction <0.001). For each 5-kg weight gain between age 18 and the year 1980, the risk of diabetes was increased by 84% (95% CI 58-114) for Asians, 44% (26-63) for Hispanics, 38% (28-49) for blacks, and 37% (35-38%) for whites. A healthy diet high in cereal fiber and polyunsaturated fat and low in trans fat and glycemic load was more strongly associated with a lower risk of diabetes among minorities (RR 0.54 [95% CI 0.39-0.73]) than among whites (0.77 [0.72-0.84]). The risk of diabetes is significantly higher among Asians, Hispanics, and blacks than among whites before and after taking into account differences in BMI. Weight gain is particularly detrimental for Asians. Our data suggest that the inverse association of a healthy diet with diabetes is stronger for minorities than for whites.