Objective: Periprostatic nerve block (PPNB) and intrarectal local anesthesia (IRLA) are two of the most commonly used methods for pain control inthe transrectal ultrasonography (TRUS)-guided prostate needle biopsy procedure, which is the standard method for the diagnosis of prostate cancer.This study compared the efficacy of IRLA alone and with PPNB using lidocaine or prilocaine.Materials and Methods: A total of 64 patients with suspicious rectal examination symptoms and/or serum prostate-specific antigen (PSA) elevationunderwent standard 12-core TRUS-guided prostate needle biopsy. The patients were divided into 3 groups: IRLA with lidocaine gel only (group 1),IRLA with lidocaine gel plus PPSB with 2% lidocaine injection (group 2), and IRLA with lidocaine gel plus PPSB with 2% prilocaine injection (group3). Patients’ pain levels were assessed by visual analog scale (VAS) immediately (VAS-1) and at 45 minutes (VAS-2) after prostate biopsy. In addition,serum PSA levels, age, body mass index (BMI), prostate volume, and cancer detection rates of the patients were recorded.Results: There were no statistical differences between the groups in terms of total PSA, age, BMI, prostate volume, or cancer detection rates.According to VAS-1 score, group 1 had more severe pain compared to the other groups, while there was no significant difference between groups 2and 3. When VAS-2 score was examined, group 1 experienced the most severe pain, while group 3 was the least painful group. When asked whichbiopsy step was the most painful, all groups reported that introduction of ultrasound probe into the rectum was the most painful.Conclusion: The combination of IRLA and PPNB seems to be a more effective method than IRLA alone for pain control during TRUS-guided prostatebiopsy. Prilocaine and lidocaine have comparable onset but the effect of prilocaine lasts longer. Therefore, prilocaine is a preferable agent for prostatebiopsy under TRUS guidance.