Objective: To determine the efficacy of intrarectal lidocaine gel alone and a combination of lidocaine gel with 2 different longer-acting local anesthetic (LA) agents that were injected into the periprostatic area before transrectal ultrasound-guided prostate biopsy. Patients and Methods: One hundred patients undergoing transrectal prostate biopsy were randomized into 4 groups of 25 patients each. Before the biopsy, group 1 received no local anesthesia, group 2 received 2% lidocaine gel intrarectally, group 3 received intrarectal lidocaine gel and 5 ml bupivacaine (0.25%) injected into periprostatic area, and group 4 received lidocaine gel intrarectally and a 5-ml ropivacaine injection (0.25%) in the same location as group 3. Pain levels during and after the biopsy were assessed by using a 10-point linear visual analog scale (VAS). Results: Patients in groups 3 and 4 had significantly lower VAS scores than those in groups 1 and 2, both during and 1 h after biopsy. There were no differences in the pain scores between groups 1 and 2. Conclusion: The combination of intrarectal lidocaine gel and periprostatic longer-acting LA agents significantly reduces the pain related to prostate biopsy, whereas intrarectal lidocaine gel administration alone does not reduce pain. Thus, administration of the periprostatic longer-acting LA agents alone is adequate. © 2009 S. Karger AG, Basel.