Background: Although early reviews of clinical findings were mostly negative, there is still a widespread belief for the efficacy of preemptive analgesia among clinicians. In this study, we evaluated whether the preemptive use of ketamine decreases post operative pain in patients undergoing appendectomy. Methods: In double-blind, randomized clinical trials, 80 adult male patients undergoing an operation for acute appendicitis were studied. Patients were randomly assigned to two groups. In the operating room, patients in the ketamine group received 0.5 mg/kg of ketamine IV 10 minutes before the surgical incision. In the control group, 0.5 mg/kg of normal saline was injected. The pain intensity was assessed at time 0 (immediately after arousal) and 4, 12, and 24 hours postoperatively using the 10 points visual analogue scale (VAS). Results: Eighty patients (40 for both groups) were enrolled in this study. For all of the evaluated times, the VAS score was significantly lower in the ketamine group compared to the control. The interval time for the first analgesic request was $23.1{pm}6.7$ minutes for the case group and $18.1{pm}7.3$ minutes for the control (P = 0.02). The total number of pethidine injections in the first 24 hours postoperatively was $0.6{pm}0.6$ for the case group and $2.0{pm}0.8$ for the controls (P = 0.032). There were no drug side effects for the case group. Conclusions: A low dose of intravenously administered ketamine had a preemptive effect in reducing pain after appendectomy.