PURPOSE: Whole grains may offer protection from diabetes by decreasing energy intake, preventing weight gain, and direct effects on insulin resistance. This study examined associations of whole and refined grains with incident type 2 diabetes (T2D) ascertained by self-reported medication use in a cohort of postmenopausal women. METHODS: We included 72,215 women free of diabetes at baseline from the Women's Health Initiative Observational Study. Whole grain consumption was categorized as 0, less than 0.5, 0.5 to 1.0, 1.0 to less than 1.5, 1.5 to less than 2.0, and 2.0 or more servings per day. Proportional hazards regression was performed to estimate hazard ratios (HR) and 95% confidence intervals adjusting for potential confounders. RESULTS: There were 3465 cases of incident T2D over median follow-up of 7.9 years. Adjusted for age and energy intake per day, successively increasing categories of whole grain consumption were associated with statistically significant reduced risk of incident T2D (HRs, 1.00, 0.83, 0.73, 0.69, 0.61, and 0.57; P for trend < 0.0001). Results were attenuated after adjustment for confounders and other dietary components. The reduction in risk of T2D was greater among nonsmokers and those who maintained their weight within 5 pounds with higher consumption of whole grains than smokers and women who gained more weight. CONCLUSIONS: This large, prospective study found an inverse dose-response relationship between whole grain consumption and incident T2D in postmenopausal women.