BACKGROUND: The aim of the current study was to evaluate the relation between physical activity and prostate cancer risk with specific emphasis on interaction with body mass index (BMI) and baseline energy intake. METHODS: The association between prostate cancer and physical activity was evaluated in the Netherlands Cohort Study, conducted among 58,279 men ages 55 to 69 years at entry. Information regarding baseline nonoccupational physical activity, history of sports participation, and occupational physical activity was collected with a questionnaire in 1986. After 9.3 years, 1,386 incident prostate cancer cases were available for case-cohort analyses. Multivariate incidence rate ratios (RR) and corresponding 95% confidence intervals (95% CI) were calculated using Cox regression analyses. RESULTS: Neither baseline nonoccupational physical activity (RR, 1.01; 95% CI, 0.81-1.25 for >90 versus <30 minutes per day), history of sports participation (RR, 1.04; 95% CI, 0.90-1.22 for ever versus never participated), nor occupational physical activity (RR, 0.91; 95% CI, 0.70-1.18 for >12 versus <8 KJ/min energy expenditure in the longest held job) showed an inverse relation with prostate cancer risk. We found an increased risk of prostate cancer for men who were physically active for >1 hour per day in obese men (BMI > 30) and men with a high baseline energy intake. DISCUSSION: The results of this current study do not support the hypothesis that physical activity protects against prostate cancer in men.