We assessed the effect of periprostatic nerve blockade during transrectal ultrasound of the prostate prior to obtaining systematic needle biopsies and the discomfort associated with this procedure. A prospective randomized study was performed on 100 men requiring systematic needle biopsy of the prostate. Patients were assigned to two groups: Group 1 received no local anesthesia and Group 2 received a periprostatic injection of 5 ml 1% lidocaine solution (2.5 ml bilaterally) prior to undergoing biopsy of the prostate. The patients were asked to respond to a pre-and post-procedural questionnaire which consisted of four questions designed to evaluate pain perception and pain experienced, respectively, during the entire procedure. Mean pain scores for Group 1 responses vs Group 2 responses were not statistically different for any of the pre-procedural questions. Post-procedural pain scores were significantly lower in Group 2 vs Group 1 (control) for questions 1 and 3: question 1 (2.6 AE 1.8 vs 3.8 AE 1.8, P < 0.05), question 2 (3.0 AE 1.9 vs 3.7 AE 2.1, P ¼ 0.14). Question 3 (2.8 AE 2.0 vs 4.3 AE 1.9, P < 0.05), and question 4 (1.6 AE 2.4 vs 2.1 AE 2.6, P ¼ 0.38). During the study, no patient from Group 2 experienced any adverse reaction from the injection. Our data suggest that periprostatic nerve blockade during transrectal ultrasound of the prostate results in less patient discomfort.