We designed this prospective, randomized, double-blinded, placebo-controlled study to compare the perioperative effects of different doses of melatonin and midazolam. Doses of 0.05, 0.1, or 0. 2 mg/kg sublingual midazolam or melatonin or placebo were given to 84 women, approximately 100 min before a standard anesthetic. Sedation, anxiety, and orientation were quantified before, 10, 30, 60, and 90 min after premedication, and 15, 30, 60, and 90 min after admission to the recovery room. Psychomotor performance of the patient was evaluated at these times also, by using the digit-symbol substitution test and Trieger dot test. Patients who received premedication with either midazolam or melatonin had a significant decrease in anxiety levels and increase in levels of sedation preoperatively compared with control subjects. Patients in the three midazolam groups experienced significant psychomotor impairment in the preoperative period compared with melatonin or placebo. After operation, patients who received 0.2 mg/kg midazolam premedication had increased levels of sedation at 90 min compared with 0.05 and 0. 1 mg/kg melatonin groups. In addition, patients in the three midazolam groups had impairment of performance on the digit-symbol substitution test at all times compared with the 0.05 mg/kg melatonin group. Premedication with 0.05 mg/kg melatonin was associated with preoperative anxiolysis and sedation without impairment of cognitive and psychomotor skills or affecting the quality of recovery. Implications: Premedication with 0.05 mg/kg melatonin was associated with preoperative anxiolysis and sedation without impairment of cognitive and psychomotor skills or affecting the quality of recovery.