Introduction The purpose of this study was to determine the effectiveness and harms of periprostatic block compared with other interventions in patients with clinically suspected prostate cancer who underwent transrectal biopsy to diminish pain. Material and methods We included only clinical trials which involved male adults older than 18 years-old suspected of having prostate cancer. The intervention performed was a periprostatic block and the comparators were topical anesthetics, sedatives, placebo/no intervention or combined therapies. The primary outcome was perianal or perineal pain and serious adverse effects (SAE). Literature search was conducted in MEDLINE, EMBASE, LILACS, CENTRAL and non-published literature from inception to March 2019. We performed a network meta-analysis in R. Results We included 43 studies in the meta-analysis. Thirteen studies compared periprostatic block vs. placebo/no intervention (the most frequent). Most of the studies had an unclear risk of bias for selection, performance and detection bias and low risk for attrition, reporting and other bias. Periprostatic block (lidocaine) + intrarectal gel (lidocaine + prilocaine) vs. periprostatic block (lidocaine) showed an RR -0.9 (95%CI – 1.9 to 0.074); intrarectal gel (lidocaine) vs. periprostatic block (lidocaine) had a RR 0.77 (95%CI 0.14 to 1.4); placebo/no intervention vs. periprostatic block (lidocaine) + intrarectal gel (lidocaine+prilocaine) RR 3 (95%CI 1.9 to 4); intrarectal gel (lidocaine) versus periprostatic block (lidocaine) + intrarectal gel (lidocaine + prilocaine) RR 1.7 (95%CI 0.64 to 2.7). Conclusions The blockage of the periprostatic plexus in the performance of a transrectal ultrasound-guided prostatic biopsy, alone or in combination with intrarectal analgesia or sedation, is an effective method to reduce pain.