The objective of the present review was to evaluate the effect of population-based screening on the incidence of prostate cancer, prostate cancer tumor stage and grade, prostate cancer mortality, and overall mortality. A systematic review was carried out in April 2011, searching the Medline and Web of Science databases. The records were reviewed to identify comparative and randomized controlled trials evaluating the effect of screening on prostate cancer. Eight trials were identified containing personalized data on a screened versus a non-screened cohort. Prostate-specific antigen and digital rectal examination were the main screening tools. Prostate-specific antigen threshold and screening interval was not uniform among the different trials. Screening was associated with a significant increase in prostate cancer detection (relative risk 1.55; P=0.002), and a significant shift towards more localized (relative risk 1.81; P=0.01) and more low-grade tumors (relative risk 2.32; P=0.001). In overall analysis, no significant effect on prostate cancer mortality (relative risk 0.88; P=0.18) and overall mortality (relative risk 0.90; P=0.27) in favor of screening was observed. An adjusted analysis excluding papers with short follow up, high prostate-specific antigen contamination in the non-screening group and low participation in the screening group was able to show a significant reduction in prostate cancer mortality of 24%. The ideal screening strategy is unclear. Screening is associated with better PC detection and this in a more localized stage and of less aggressive tumors. Excluding the main shortcomings in screening studies (short follow up, high prostate-specific antigen contamination in non-screening group and low participation in screening group), screening is able to reduce prostate cancer mortality.