The objective of the present study was to evaluate the efficacy of the periprostatic nerve block (PNB) of the prostate-vesicular junction with low volume and high concentration of anesthetics in relieving pain during prostate biopsy. Two hundred and twenty patients were enrolled and randomized to receive PNB with 5 ml 2% lidocaine (group 1110 pts) and PNB with 5 ml 2% mepivacaine (group 2, 110 pts). The anesthetic was administered through a single puncture on each side at the prostate-vesicular junction using a 22-gauge needle. All patients filled in a ten visual analogue pain score scale (VAS) from 0 = no discomfort to 10 = severe pain, for the assessment of pain experienced during biopsy. The two groups were homogeneous concerning the anthropometrical data. The mean pain score with lidocaine was 1.4 +/- 1.02 (CI 95% = 1.53 to 3.57) and with mepivacaine was 1.3 +/- 1.06 (CI 95% = 2.66 +/- 4.84) with no statistical significant difference between groups (p = 0.43). No general or local adverse effects were observed between the anaesthetics. The use of a low volume (2.5 ml on each side) and high concentration (2%) of local anesthetics (lidocaine/mepivacaine) almost completely suppresses pain and discomfort associated with prostate biopsy. The anatomy of neurovascular bundle regions appears favourable to the administration of small amounts of anesthetic.