Melatonin has emerged as an anti-inflammatory agent, potent direct free-radical scavenger, and an indirect antioxidant in preventing ischemia-reperfusion injury. This study aimed to evaluate melatonin's effect on cardiac biomarkers after coronary artery bypass grafting (CABG). A double-blind, randomized placebo-controlled pilot clinical study. Booali Sina Hospital, Qazvin University of Medical Sciences, Qazvin, Iran. One hundred patients undergoing elective CABG. The patients were divided randomly into control (C) and melatonin (M) groups (50 patients per group). The M group received 3 mg of melatonin the night before surgery, 3 mg in the morning, and routine cardiac surgery medications. The C group received 1 placebo tablet rather than melatonin. After surgery, the patients in the M group received 3 mg of melatonin, and the C group received 1 placebo tablet at bedtime until the third day after CABG. In both groups, creatine kinase-MB (CPK-MB), cardiac troponin I, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) were measured before surgery and on the first, second, and third postoperative days. Serum CPK-MB levels on the second and third day after CABG were significantly lower in the M group than in the C group (p < 0.05). Regarding cardiac troponin I, CRP, and ESR markers, there were no significant changes in serum concentration before surgery and on the first, second, and third days after surgery between the 2 groups (p > 0.05). The mean length of hospitalization in the ICU was lower in the M group (3.4 ± 1.05) compared with the C group (3.96 ± 1.06, p = 0.01). Melatonin reduced the postoperative level of CPK-MB and the length of hospitalization in the ICU in patients who underwent cardiac surgery. [ABSTRACT FROM AUTHOR]