Myocardial ischemia/reperfusion injury represents a clinically critical problem associated with coronary artery bypass graft surgery (CABG). The degree of oxidative stress, inflammation and apoptosis are increased during the reperfusion of the heart muscles following ischemia. The present study aims to examine the protective role of melatonin in ameliorating the degree of cardiac injury in patients undergoing bypass surgery, and whether this effect is a dose related.A total of forty-five patients who were undergoing elective CABG in (Al-Najaf Cardiac Center, Al-Najaf, Iraq) were included in this study for the period between January, 2015 and November, 2015. Participants were randomly allocated into 3 study groups: Placebo-controlled group (C), low dose melatonin treatment group, 10mg capsule once daily (M1) and high dose melatonin treatment group 20mg capsule once daily (M2).Compared to the control group, there was a significant increase in the ejection fraction (EF%) associated with a significant decline in heart rate (HR) among the M1 and M2 groups compared to the C group (P<0.05). In addition, there was a significant reduction in plasma levels of cardiac Troponin-I (CTnI), interleukin-1beta (IL-1β), Inducible nitric oxide synthase (iNOS) and caspase-3 enzymes in the melatonin groups (group M1 and M2) compared to the control group, (P<0.05) in Melatonin-treated groups. Comparing the two melatonin study groups, the changes in the parameters mentioned above were more significant in the M2 group compared to the M1 group (P<0.05).These findings suggested that melatonin supplementation can ameliorate the degree of myocardial ischemic-reperfusion injury, dose dependent effects.