Background: delirium is a common complication after cardiac surgical procedures and is associated with increased morbidity and mortality. Postoperative delirium is associated with an increased length of stay in the intensive care unit, long hospital stay and high hospital charges. Aim of the Work: to investigate the effectiveness of melatonin as a preoperative sedative as well as the preventive and the curative effect of melatonin supplementation in elderly patients undergoing coronary artery bypass surgery on postoperative delirium. Patients and Methods: this prospective, randomized, controlled, double blind study was conducted on a total of 50 patients allocated into 2 equal groups. It was conducted in Ain Shams University hospitals, in the cardiothoracic surgery unit. Results: melatonin has superior sedative effect at 30 min preoperatively compared with placebo (P=0.022). Melatonin succeeded to treat about 56% of delirious patients. The incidence of delirium was 8% in the melatonin group vs. 28% in the control group (P= 0.046). In univariate analysis, predictors of delirium in both groups were age (P= 0.049 in melatonin group, P=0.021 in control group), higher fentanyl dose (P= 0.021 in melatonin group, P=0.047 in control group), lower ejection fraction (P= 0.018 in melatonin group, P=0.008 in control group), longer cardiopulmonary bypass (CPB) times (P= 0.026 in melatonin group, P=0.04 in control group) and longer aortic cross clamping (ACC) times (P= 0.04 in melatonin group, P=0.019 in control group). Conclusion: administration of melatonin significantly decreased the incidence of postoperative delirium (POD) after coronary artery bypass grafting in elderly patients and significantly increased preoperative sedation. Advanced age, higher total intraoperative fentanyl dose, lower ejection fraction and longer CPB and ACC times were independent predictors of POD with or without melatonin supplementation.