Few studies have examined differences in endometrial cancer risk among ethnic groups in the United States. The authors assessed the extent to which known risk factors for endometrial cancer explain the racial/ethnic differences in risk among 46,933 postmenopausal African-American, Native-Hawaiian, Japanese-American, Latina, and White women recruited to the prospective Multiethnic Cohort Study in 1993-1996. During a 7.3-year follow up period, 321 incident endometrial cancer cases were identified among these women. Data on known/suspected risk factors were obtained from baseline questionnaires, and comparisons of endometrial cancer incidence across racial/ethnic groups were estimated using log-linear proportional hazard models. Later age at menopause, unopposed estrogen therapy use, and obesity were associated with increased risk, while increasing parity and increasing duration of oral contraceptive use were associated with decreased risk. The relative risks for endometrial cancer (vs. Whites) were 0.76 (95% confidence interval (CI): 0.53, 1.08) for African Americans, 0.92 (95% CI: 0.58, 1.46) for Native Hawaiians, 0.61 (95% CI: 0.46, 0.83) for Japanese Americans, and 0.63 (95% CI: 0.46, 0.87) for Latinas. After adjustment for the risk factors, the relative risks were 0.68 (95% CI: 0.47, 0.98) for African Americans, 0.91 (95% CI: 0.56, 1.46) for Native Hawaiians, 0.74 (95% CI: 0.54, 1.01) for Japanese Americans, and 0.65 (95% CI: 0.47, 0.92) for Latinas. Results from this study show that the interethnic differences in endometrial cancer risk do not appear to be explained by differences in the distribution of known risk factors among women of different races/ethnicities.