PURPOSE Since the introduction of prostate specific antigen (PSA) screening, asymptomatic men often undergo transrectal ultrasound guided prostate biopsy. This procedure may cause significant discomfort, which may limit the number of biopsies. We performed a randomized prospective study to compare periprostatic infiltration with 1% lidocaine with intrarectal instillation of 2% lidocaine gel before prostate biopsy. MATERIALS AND METHODS From October 1999 to July 2000, 150 men underwent prostate biopsy at the Miami Veterans Administration and Jackson Memorial Hospital. Experienced senior residents performed all biopsies. Patients were randomized into 2 groups depending on the method of anesthetic delivery. A visual analog scale was used to assess the pain score. Statistical analysis of pain scores was performed using the Student t test. RESULTS Ultrasound guided prostate biopsy was done in 150 cases. There was a statistical difference in the mean pain score after periprostatic infiltration and intrarectal instillation (2.4 versus 3.7, p = 0.00002) with patients receiving periprostatic infiltration reporting significantly less pain. CONCLUSIONS Men should have the opportunity to receive local anesthesia before ultrasound guided prostate biopsy with the goal of decreasing the discomfort associated with this procedure. Our prospective randomized study indicates that ultrasound guided periprostatic nerve block with 1% lidocaine provides anesthesia superior to the intrarectal placement of lidocaine gel.