Background Dietary energy density, or energy available in relation to gram intake, can inform disease risk. Objective The objective of this study was to investigate the association between baseline dietary energy density and risk of incident type 2 diabetes in postmenopausal women. Design Dietary energy density, weight status, and type 2 diabetes incidence were prospectively characterized in a large cohort of postmenopausal women participating in one or more clinical trials or an observational study. Participants/setting The study involved 161,808 postmenopausal women recruited to the Women's Health Initiative observational study or clinical trials at 40 centers across the United States between 1993 and 1998. Main outcome measures The primary outcome was incident type 2 diabetes. Statistical analyses performed The association between dietary energy density quintiles and incident diabetes was tested using Cox proportional hazards regression. Results A total of 143,204 participants without self-reported diabetes at enrollment completed baseline dietary assessment and were followed for 12.7 +/- 4.6 years. Risk of diabetes developing was 24% greater for women in the highest dietary energy density quintile compared with the lowest after adjusting for confounders (95% Cl 1.17 to 1.32). Body mass index (calculated as kg/m(2)) and waist circumference mediated the relationship between dietary energy density and diabetes. In waist circumference stratified analysis, women in dietary energy density quintiles 2 to 5 with waist circumferences >88 cm were at 9% to 12% greater risk of diabetes developing compared with women with waist circumference <88 cm. Conclusions In this prospective study, a higher baseline dietary energy density was associated with higher incidence of type 2 diabetes among postmenopausal women, both overall, and in women with elevated waist circumference.