Abstract BACKGROUND: Atrial fibrillation (AF) occurs often in patients after coronary artery bypass grafting (CABG) and can result in increased morbidity and mortality. The purpose of this study is to compare the prophylactic effect of Amiodarone versus Propranolol in patients with various levels of ejection fraction. METHODS: In a randomized double-blinded clinical trial, 110 patients received either Amiodarone (n=65) or propanolol (n=65). Adult patients of either sex and age of 40-75 years were considered for participation when listed for nonemergent CABG surgery and bypass without other concomitant procedures. Amiodarone was given as 150 mg single dose 30 min after procedure through 48 hours. In addition, Amiodarone was also administered intravenously during surgery in a 300-mg bolus for 1 h and as a total maintenance dose of 20 mg/kg weight over 24 h on the first day following surgery. Propanolol was given as 10 mg oral single dose immediately after surgery and continued for long term operation. RESULTS: The primary endpoint was the occurrence of AF after CABG. The secondary endpoint was the hospitalization length of stay after CABG. The baseline characteristics were similar in both treatment groups. The incidence of post-operative AF was significantly higher in the Propranolol group compared with the Amiodarone group (4 vs 12.2 % of patients with low EF, P<0.0001). The durations of postoperative intensive care unit stays were the same in the Amiodarone and Propranolol groups (2±0.7 vs. 3.5±0. 5 days, P<0.001). CONCLUSION: This study demonstrates that postoperative course of Amiodarone administration is an effective, possibly safe, well-tolerated, and widely applicable therapy for the prevention of postoperative atrial tachyarrhythmia after cardiac surgery. This benefit was associated with a reduction in the probability of preoperative sustained ventricular tachyarrhythmia and a trend toward a reduction in postoperative hospital stay. Keywords: Atrial Fibrillation, Coronary Artery Bypass Grafting, Amiodarone, Propranolol.