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Transrectal Ultrasound (TRUS) guided prostate biopsy is regarded as the gold standard for prostate cancer diagnosis. The majority of patients perceive TRUS-guided prostate biopsy as a physically and psychologically traumatic experience. We aimed to compare in this paper the efficacy of three different anesthesia techniques to control the pain during the procedure. Materials and methods: 150 patients who underwent transrectal ultrasound (TRUS) guided prostate biopsy were randomly divided into three groups. Group A included 50 patients who received one hour before the procedure a mixture of 2.5% lidocaine and 2.5% prilocaine, Group B: 50 patients who received intrarectal local anesthetic administration (lidocaine 5 ml 10%) and lidocaine local spray 15 % and Group C included 50 patients who received periprostatic block anesthesia (lidocaine 10 ml 10%). Visual analogue scale (VAS) of patients in different groups was evaluated at the end of the biopsy and 30 minutes after the procedure. Results: The VAS of patients in Group A was 1.32 ± 0.65 (VAS I) and 2.47 ± 0.80 (VAS II). In group B the VAS of patients was 1.09 ± 0.47 (VAS I) and 1.65 ± 0.61 (VAS II). In group C the VAS of patients was 2.63 ± 0.78 (VAS I) and 1.70 ± 0.85 (VAS II). There was no statistically significant difference in term of VAS I between group A and B. A statistically significant difference was determined in terms of VAS II between group A and B. There was no statistically significant difference in term of VAS between group B and C. Conclusions: The most effective of the three methods for pain control we used was intrarectal local anesthetic administration and lidocaine local spray 15% that enables an ideal patient comfort.