We evaluated whether pelvic plexus block (PPB) is superior to periprostatic nerve block (PNB) for pain control during transrectal ultrasonography (TRUS)-guided prostate biopsy (PBx). A prospective, double-blind, randomized, controlled study was performed at a single center; 46 patients were enrolled and randomly allocated into two groups: PPB (n = 23) and PNB (n = 23). The visual analogue scale (VAS) was used; pain scores were measured four times: during local anesthesia, probe insertion, sampling procedures, and at 15 min post procedures. No significant differences were observed in VAS scores during local anesthesia (2.30 for PPB vs. 2.65 for PNB, p = 0.537) or during probe insertion (2.83 for PPB vs. 2.39 for PNB, p = 0.569). Similarly, no differences in VAS scores were detected during the sampling procedures (2.83 for PPB vs. 2.87 for PNB, p = 0.867) and at 15 min post procedures (1.39 for PPB vs. 1.26 for PNB, p = 0.631). No major complications were noted in either group. Both PPB and PNB are comparably effective and safe methods for PBx related pain relief, and PPB is not superior to PNB. Local anesthetic method could be selected based on the preference and skill of the operator.