The aim of this study was to compare the effects of prophylactic dronedarone and amiodarone in prevention of arrhythmias during and following off-pump coronary artery bypass grafting (OPCAB). This randomized, controlled, double-blinded, parallel-group study was carried out on 36 adult male patients aged 30-70 years, with modified Parsonnet score 0-10 undergoing offpump coronary artery bypass grafting. After obtaining approval from the institutional ethics committee and informed consent, the patients were randomly allocated to two equal groups (n=18). In one group, patients were given inj. amiodarone 3mg/kg in 100ml of normal saline prior to skin incision intravenously over 20 minutes. In the second group patients received tablet dronedarone 400mg orally twice daily, commencing three days prior to the date of surgery. Patients in the amiodarone group received placebo tablet while patients in the dronedarone group received placebo infusion for the sake of blinding. The frequency and profile of arrhythmias intraoperatively and 24 hours postoperatively were studied. Intraoperative arrhythmias occurred in 50% of patients receiving amiodarone and 16.67% of patients receiving dronedarone. Maximum ventricular rate during atrial fibrillation was significantly lower in the dronedarone group (121 beats per min) than in the amiodarone group (168 beats per min). The study concludes that dronedarone appears to be at least as effective as amiodarone in prophylaxis of intraoperative and postoperative arrhythmias in patients undergoing OPCAB, with a better control of ventricular response.