Context Numerous observational epidemiologic studies have evaluated the association between physical activity and prostate cancer (PCa); however, the existing results are inconsistent. Objective To determine the association between physical activity and risk of PCa. Evidence acquisition A systematic search was performed using the Medline, Embase, and Web of Science databases through 15 May 2011 to identify all English-language articles that examined the effect of physical activity on the risk of PCa. This meta-analysis was conducted according to the guidelines for the meta-analysis of observational studies in epidemiology. Evidence synthesis This meta-analysis consisted of 88 294 cases from 19 eligible cohort studies and 24 eligible case-control studies. When data from both types of studies were combined, total physical activity (TPA) was significantly associated with a decreased risk of PCa (pooled relative risk [RR]: 0.90; 95% confidence interval [CI], 0.84–0.95). The pooled RR for occupational physical activity (OPA) and recreational physical activity (RPA) were 0.81 (95% CI, 0.73–0.91) and 0.95 (95% CI, 0.89–1.00), respectively. Notably, for TPA, we observed a significant PCa risk reduction for individuals between 20 and 45 yr of age (RR: 0.93; 95% CI, 0.89–0.97) and between 45 and 65 yr of age (RR: 0.91; 95% CI, 0.86–0.97) who performed activities but not for individuals <20 yr of age or >65 yr of age. Conclusions There appears to be an inverse association between physical activity and PCa risk, albeit a small one. Given that increasing physical activity has numerous other health benefits, men should be encouraged to increase their physical activity in both occupational and recreational time to improve their overall health and potentially decrease their risk of PCa.