Prostate cancer is the second most common cancer in men worldwide, and sedentary behavior is widespread, yet reviews and meta-analyses summarizing the role of sedentary behavior as a potential risk factor for prostate cancer are scarce. We searched PubMed, Web of Science, and Cochrane databases for relevant articles up to January 2019. We pooled maximally adjusted risk estimates in a random effects model and performed meta-regression meta-analysis, assessed heterogeneity and publication bias using , funnel plots, and Egger and Begg tests, and conducted sensitivity analyses and influence diagnostics. Data from 12 prospective cohort studies including a total of 30,810 prostate cancer cases were analyzed. We found no statistically significant association between high versus low sedentary behavior and prostate cancer incidence [RR = 1.07; 95% confidence interval (CI), 0.99-1.16; 0.10]. We noted that adjustment for body mass index (BMI) modified the relation of sedentary behavior to prostate cancer, particularly aggressive cancer. Sedentary behavior was related to a statistically significant increased risk of aggressive prostate cancer in analyses not adjusted for BMI (RR = 1.21; 95% CI, 1.03-1.43), whereas no association was apparent in BMI-adjusted analyses (RR = 0.98; 95% CI, 0.90-1.07), and the difference between those summary risk estimates was statistically significant ( = 0.02). Sedentary behavior is not independently associated with prostate cancer. However, prolonged sedentary behavior may be related to increased risk of aggressive prostate cancer through a mechanism involving obesity. This finding represents a potentially important step toward considering sedentary behavior as a modifiable behavioral risk factor for aggressive prostate cancer.