Background Atrial fibrillation (AF) is one of the most common arrhythmia after coronary artery bypass grafting (CABG), which not only increases the suffering of the patients, but also prolongs hospital stay and enhances cost of care, especially for patients older than 70 years. This study was designed to evaluate the efficacy and safety of low-dose amiodarone in the prevention of AF after CABG, especially for the elderly.Methods Two hundred and ten senile patients undergoing off-pump CABG were included in this prospective, randomized, double-blind and placebo controlled study. Patients were given 10 mg/kg of amiodarone (low-dose amiodarone group, n=100) or placebo (control group, n=110) daily for 7 days before surgery and followed by 200 mg of amiodarone or placebo daily for 10 days postoperatively.Results Postoperative AF occurred in 16 patients (16%) receiving amiodarone and in 36 (37.7%) patients receiving placebo (P=0.006). AF occurred at (58.13±16.63) hours after CABG in the low-dose amiodarone group and at (45.03±17.40) hours in the control group (P=0.018). The maximum ventricular rate during AF was significantly slower in the low-dose amiodarone group ((121.42±28.91) beats/min) than in the control group ((134.11 ±30.57) beats/min, P=0.036). The duration of AF was (10.92±9.56) hours for the low-dose amiodarone group compared with (14.81 ±10.37) hours for the control group (P=0.002). The postoperative left ventricular ejection fraction (LVEF) was significantly improved in the low-dose amiodarone group (from (59.9 ±10.3)% to (63.4±11.4)%, P=0.001), and significantly higher compared with the control group ((58.5±10.7)%, P=0.002). Both groups had a similar incidence of complication other than rhythm disturbances (12.0% vs 16.4%, P=0.368). The low-dose amiodarone group patients had shorter hospital stays ((11.8±3.2) days vs (13.8±4.7) days, P=0.001) and lower cost of care (RMB (79 115±16 673) Yuan vs RMB (84 997±21 587) Yuan, P=0.031) than that of control group patients. The in-hospital mortality was not significantly different between the two groups (1.0% vs 0.9%, P=0.946).Conclusions Perioperative low-dose oral amiodarone appeared to be cost-effective in the prevention and delay of new-onset postoperative AF in aged patients. It significantly reduced ventricular rate and duration of AF after CABG, decreased hospital cost and stay, as well as promoted the amelioration of left ventricular systolic function. Furthermore, low-dose amiodarone was safe to use and well tolerated with low toxic and side effects, and did not increase the risk of complications and mortality. It is proved to be a first-line therapy and as routine prophylaxis for AF after CABG, especially for elderly patients complicated with left ventricular dysfunction.