Objective: To examine the physical activity and endometrial cancer relationship in a prospective study of US women enrolled in the Breast Cancer Detection Demonstration Project (BCDDP) Follow-up Study. Methods: We assessed past-year physical activity of all types in 23,369 women who returned the baseline questionnaire (1987–1989) and had no prior hysterectomy and/or endometrial cancer. Cox proportional hazards models were used to estimate age, education, and parity-adjusted rate ratios (RR) and 95% confidence intervals (CI) for the 253 confirmed endometrial cancer cases identified during an average 8.2 years of follow-up (ending 1995–1998). Results: There were no dose–response relationships with either total or vigorous physical activity; however, compared to the lowest total activity quartile, the higher four quartiles had a non-significantly lower risk (RR = 0.8, CI = 0.6–1.0). The association with moderate activity varied with follow-up time: RRs (CI) for a 1 h increase in daily moderate activity within 2-year intervals of follow-up (≤2, 2.1–4.9, 5.0–8.0, >8 years) were 1.1 (1.0, 1.2), 1.0 (0.9, 1.1), 1.0 (0.9, 1.1), 1.0 (0.9, 1.1), and 0.8 (0.7, 1.0), respectively. Conclusion: These data suggest that recent physical activity is not strongly related to the risk of endometrial cancer, and that prolonged exposure and longer follow-up may be necessary.