Backgrounds: Brief noxious stimuli are found to produce long-lasting neuronal sensitization. This cumulative depolarization results from the activation by glutamate of N-methyl-D-aspartic acid (NMDA) receptor. Ketamine at subanesthetic doses blocks the channel associated with the NMDA receptor. The aim of this study was to investigate the pre-emptive effect of ketamine in children after circumcision with unilateral hydrocelectomy. MATERIALS AND METHODS: We have compared the effect of preoperative ketamine (0.3 mg/kg) in a double-blind, randomized study, which was approved by the local Ethics Committee. Informed consents were obtained from their parents. After induction of anesthesia, patients were allocated randomly to receive a ketamine (n=20) or placebo (n=20) intravenously before surgery. Postoperative pain was rated on a faces scale for the first 24 hours. If pain occurred, children received tiaprofenic acid in a dose related to body weight. The cumulative pain score, the time of the first requirement of analgesics, and total requirement of analgesics for 24 hours were also checked. RESULTS: The pain scores at 4, 5, 6, 7, 8, 9, and 12 hours after operation were significantly low in ketamine group. The cumulative pain scores for the first 8 hours and the total requirements of analgesics were significantly low in ketamine group. The time of the first requirement of analgesic was significantly delayed in ketamine group. CONCLUSIONS: Preoperative ketamine in the pediatric circumcision with unilateral hydrocelectomy is effective on the reducing the intensity of the postoperative pain. The results of this study support the theory of pre-emptive analgesia of ketamine.