Background: Myocardial infarction that occurs during surgery for cardiac patients is still a difficult issue that raises morbidity and mortality. Clinical investigations demonstrate that nocturnal melatonin secretion is lowered in individuals with Alzheimer's disease, coronary heart disease, and stroke, although the pathophysiologic implications of altered melatonin secretion remain unclear. Aim: The current study aimed to evaluate the protective role of melatonin in improving the degree of cardiac injury in patients undergoing bypass surgery. Patients & Methods: This is a randomized control clinical study, which took place in Suez Canal University Hospital in the routine surgical theaters. Following the departmental research committee approval and informed patient's consent, 74 patients, undergoing CABG surgery were randomly allocated to one of the two groups using a table of random numbers: group M received 10 mg melatonin orally for two nights pre-operative as a study group, and group C received placebo orally for two nights pre-operative as a control group. Results:  Our result presented a substantial difference between the control and melatonin groups in post-cardiopulmonary bypass heart rate, cardiac injury enzymes as cTnI and CK MB levels, new wall motion abnormalities, cardiac systolic function EF %, and post-operative ventilation time. Conclusion: Administration of oral melatonin hormone 10 mg for two nights pre-operative can decrease myocardial I/R injury and improve outcome after CABG surgery by increasing cardiac systolic function EF%, decreasing cardiac wall motion abnormalities, decreasing cardiac injury biomarkers (CK -MB and troponin I) and decrease post-operative ventilation duration.