ABSTRACT: We aimed to compare the effectiveness of various local anesthetic methods for controlling prostate biopsy (PBx) related pain using network meta-analysis. Literature searches were performed on PubMed/Medline, Embase, and Cochrane Library up to March 2018. Forty-seven randomized controlled trials, in which the effectiveness of PBx-related pain was investigated using a visual analogue scale after various local anesthetic methods, were included. The local anesthetic methods included intraprostatic local anesthesia (IPLA), intrarectal local anesthesia (IRLA), intravenous sedation (IVS), periprostatic nerve block (PNB), pelvic plexus block (PPB), and spinal anesthesia (SPA). Eight pairwise meta-analyses and network meta-analyses with 21 comparisons were performed. All modalities, except single use of IPLA and IRLA, were more effective than placebo. Our results demonstrate that PNB + IVS (rank 1) and SPA (rank 2) were the most effective methods for pain control. The followings are in order of PPB + IRLA, PNB + IPLA, PPB, PNB + IRLA, IVS, and PNB. In conclusion, the most effective way to alleviate PBx-related pain appears to be PNB + IVS and SPA. However, a potential increase in medical cost and additional risk of morbidities should be considered. In the current outpatient setting, PPB + IRLA, PNB + IPLA, PPB, PNB + IRLA, and PNB methods are potentially more acceptable options.