BACKGROUND: Although coronary artery bypass graft (CABG) surgery has been reported to be one of the most effective internentions in terms of myocardial salvage, reperfusion itself can cause additional damage to the myocardium. Since there is strong evidence that free radicals are the principal offender in ischemia-reperfusion (I/R) injury, it has been suggested that treatment with antioxidant agents can be protective. Investigations have shown that melatonin secretion is partially disturbed in CABG patients. The aim of this study was to evaluate the protective effect of melatonin as an antioxidant agent on I/R injury.METHODS: ۱۶۴ elective CABG candidates participated in this randomized clinical trial during the preoperative period. The candidates were randomized to receive ۳ mg of melatonin tablets (physiologic dose) from ۳ days before surgery until the day of discharge. Cardiac biomarkers [troponin and creatine kinase myocardial band (CKMB)] were assessed once before surgery (۲۴ hours before surgery), and ۸ and ۲۴ hours after surgery.RESULTS: Finally, ۱۳۰ patients, ۶۵ (۵۰%) patients in the melatonin group and ۶۵ (۵۰%) in the control arm finished our study. Mean age of melatonin and control groups was ۵۹.۹۰ ± ۹.۵۹ and ۶۰.۸۰ ± ۸.۰۰ years, respectively; moreover, ۴۷ (۷۲.۳۰%) in melatonin and ۴۵ (۶۹.۲۳%) in control group were men. No significant difference was seen in baseline cardiac biomarkers between two groups (P > ۰.۰۵). In both groups, cardiac biomarkers (CKMB and troponin) elevated after surgery in comparison to their preoperative values. There was no statistically significant difference between the control and melatonin groups regarding the ۸-hour and ۲۴-hour troponin and CKMB when adjusted for interacting factors (P > ۰.۰۵).CONCLUSION: Although physiological concentration of melatonin is protective against I/R injury, substitution of endogenous melatonin with the oral supplement which creates physiologic concentration may not prevent I/R injury. In order to have antioxidant effect, pharmacologic doses of melatonin should be employed.