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Objective: This study aimed to evaluate the effectivity of pain palliation with intrarectal local anesthesia (IRLA), periprostatic nerve block (PPNB), apex nerve block (ANB), or their combination during transrectal ultrasound-guided (TRUS) prostate biopsy. Materials and Methods: A total of 160 patients who underwent TRUS biopsy were included in this prospective study. Patients were divided into three groups randomly: IRLA group (group 1, n=40), PPNB + IRLA group (group 2, n=60), and ANB + PPNB + IRLA group (group 3, n=60). Visual analog scale (VAS) was used at three separate times during prostate biopsy: on insertion of the probe through the anal canal, during the administration of anesthesia, and during needle biopsy. The pain palliation of each method was compared among the groups. Results: No significant difference was observed in demographic features among the groups. However, biopsy-related pain was the highest in group 1 for each core, followed by group 2 and group 3 (p<0.05 for all core scores). The pain level felt with local anesthesia administration was higher in group 3 than in group 2 and the lowest in group 1 (p<0.05). In addition, VAS scores were significantly higher in patients with large prostate, especially in apical cores. Conclusion: In prostate biopsy, ANB was more effective in reducing pain. ANB in patients with large prostate is considered to increase patient satisfaction by decreasing pain scores, especially in apical cores. [ABSTRACT FROM AUTHOR]