Introduction: Postoperative delirium is a common complication of cardiac surgery. This study aimed to assess the effect of supplementing dexmedetomidine infusion with oral melatonin in prevention of postoperative delirium after coronary artery bypass graft surgery. Methods: 110 patients of both sexes above 60 years of age were included. Anesthetic management was standardized. Patients were randomly allocated into one of the two study groups, dexmedetomidine/melatonin (DM) group or dexmedetomidine (D) group. Patients in the DM group received oral Melatonin tablet 5 mg the night before surgery and same dose was repeated every 24 hours for 3 postoperative days. After completion of surgery and upon ICU arrival, patients in both groups received a bolus of 0.4 µg/kg dexmedetomidine followed by 0.2-0.7 µg/kg/h infusion, for 24 maximum hours. Delirium was assessed for 5 days postoperatively at 12 hr intervals using confusion assessment method (CAM) for ICU and after discharge from ICU to surgical ward using CAM. Delirious patients were treated with IV haloperidol. Results: No significant differences between studied groups regarding baseline, preoperative, intraoperative and postoperative characteristics. Incidence of delirium was significantly lower, onset significantly more delayed, and duration was significantly shorter in group-DM as compared to group-D. No significant differences between all cases, cases who had delirium, and cases who did not have delirium in the two groups as regards extubation time, ICU stay, and hospital stay. Conclusion: supplementing dexmedetomidine with melatonin decreases incidence, delays onset, and shortens duration of postoperative delirium in patients above 60 years of age undergoing CABG surgery.