We evaluated the type and amount of physical activity associated with risk of endometrial cancer. In this population-based case-control study, in-person interviews were completed among 832 incident endometrial cancer cases and 846 age-matched controls. Physical activity from exercise, household activities, and transportation was assessed in adolescence and adulthood, as was lifetime occupational activity. Logistic regression was used to estimate adjusted odds ratios (OR) and 95% confidence limits (95% CL). Women reporting exercise participation in both adolescence and adulthood were at nearly a 40% reduced risk (OR, 0.63; 95% CL, 0.42-0.95), compared with women reporting no exercise in either life period. Postmenopausal women who initiated exercise in adulthood were also at reduced risk (OR, 0.76; 95% CL, 0.56-1.02). Reductions in risk were also observed for common lifestyle activities, including household activity (both life periods) and walking for transportation (adulthood). Examination of the independent and combined effect of exercise and lifestyle activities revealed that women with less active lifestyles but who reported exercise were at 35% reduced risk (OR, 0.65; 95% CL, 0.41-1.02), whereas nonexercisers with more active lifestyles were at 40% to 45% reduced risk. These findings suggest that both lifestyle activities of lower intensity (e.g., walking and doing household chores) and intentional exercise can reduce endometrial cancer risk.