Background: Heart surgery patients who develop acute and new-onset AF (postoperative atrial fibrillation, POAF) are among the most common postoperative complications, affecting around 35 percent of those who undergo the procedure. Objective: To assess the effectiveness of amiodarone in prophylaxis of AF post coronary artery bypass surgery (CABG). Patients and Methods: Our work represents a randomized clinical trial, which was carried out at National Heart Institute and Zagazig University from the period of August 2020 to June 2021. 68 patients, admitted for CABG and had high risk score according to POAF score, were included in our study. Results: Regarding mean left ventricular ejection fraction (LVEF), in group I was 47.52±5.85 while in group II it was 49.85±6.25. There was a statistically non-significant difference between the groups with a P value of 0.414. Mean Intensive Care Unit (ICU) period was 4.42±1.35 in group I, and group II was 2.73±0.95. The difference between the groups was statistically significantly shorter among group II (prophylaxis group) (P <0.01). Regarding development of POAF, in group I, the incidence of POAF was 85.3% while in group II, it was 38.2%. Difference among the two studied groups was statistically significantly lower in the group II (prophylaxis group). Conclusion: A prophylactic amiodarone strategy dramatically decreased incidence of POAF risk. All previous estimations of POAF risk reduction using prophylactic amiodarone were found to be accurate. Amiodarone was more effective in preventing postoperative atrial fibrillation with no serious side effects and it decreased postoperative ICU stay.