BACKGROUND: Melatonin has anxiolytic and potential analgesic effects. We assessed 0 the efficacy of melatonin premedication in reducing tourniquet-related pain and 0 improving analgesia in patients receiving IV regional anesthesia (IVRA). METHODS: Forty patients undergoing elective hand surgery under IVRA were randomly assigned into two groups (20 patients each) to receive either melatonin 10 mg (melatonin group) or placebo (control group) as oral premedication. IVRA 0 was achieved with lidocaine, 3 mg/kg, diluted with saline to a total volume of 40 mL. Anxiety scores, hemodynamic changes, sensory and motor block onset and recovery times, tourniquet pain, the quality of intraoperative anesthesia, time to first analgesic request, and 24 h analgesic requirements were recorded. RESULTS: After premedication, the anxiety scores were significantly reduced in the melatonin group (P = 0.023). During surgery, patients who received melatonin premedication had better tourniquet tolerance (lower verbal pain scores at 30, 40, and 50 min after tourniquet inflation, P < 0.05), lower rescue fentanyl requirements (15.6 +/- 21.9 vs 45.7 +/- 33.4 mu g, P = 0.002), longer time to the first postoperative analgesic request (145.4 +/- 20.2 min vs 74.6 +/- 12.8, P < 0.001) and lower postoperative didofenac consumption at 24 h (86.3 +/- 27.5 mg vs 116.3 +/- 38.3 mg, P = 0.007) compared with the control group. CONCLUSIONS: Melatonin is an effective premedication before IVRA since it reduced patient anxiety, decreased tourniquet-related pain, and improved perioperative analgesia.