The effect of body size and change in BMI on endometrial cancer risk across different racial/ethnic groups has not been studied. We examined the association between body size and endometrial cancer risk and potential effect modification of other risk factors among 50,376 women in the Multiethnic Cohort Study. During 10.3 years of follow-up, 463 endometrial cancer cases were identified. Epidemiologic data were collected from the baseline questionnaire. "BMI change" was defined as the percentage of body mass index change from age 21 to the time of recruitment. Women who were heavier at age 21 or at baseline (weight > or = 53.5 kg or > or = 63.9 kg, respectively) had an increased endometrial cancer risk compared to the lowest quartile of weight during the respective periods. BMI gain > or = 35% had a RR of 4.12 (95% CI: 2.69, 6.30) compared to the reference group (-5% < or = BMI change <+5%). Women who averaged an annual BMI gain > or = 1% had a >3.21-fold (95% CI: 2.37, 4.33) increased risk compared to women who maintained a stable adult BMI (-0.25 to <+0.25%). The highest risk associated with BMI gain was observed among nulliparous women and postmenopausal women who never used hormone therapy. Although African Americans and Whites showed an increase in risk after > or =35% BMI gain, Japanese Americans showed an increase in risk with much smaller gain (> or =5%). In conclusion, adult obesity and increase in adiposity are risk factors for endometrial cancer; and the risk associated with these factors may vary across racial/ethnic groups.