Background: Postoperative arrhythmias are an important cause of morbidity and mortality after cardiac surgery for congenital heart disease. In the early postoperative period, patients with congenital heart disease are especially vulnerable to rhythm disturbances. Objective: This study aimed to assess safety and efficacy of prophylactic amiodarone and magnesium sulphate in preventing cardiac arrhythmia especially junctional ectopic tachycardia (JET) in children with congenital heart disease (CHD) who undergo open heart surgery. Patients and Methods: This was a comparative clinical trial that was conducted on 48 cases at Cardiothoracic Department and Pediatric Cardiology Unit, Zagazig University Hospitals. The cases were divided into three groups according to received drug; Group (A): patients receiving placebo, Group (B): patients receiving magnesium sulfate and Group (C): patients receiving amiodarone. Results: There were highly statistically significant differences between groups as regard to Inotrope Score intraoperatively, heart rate and median arterial pressure postoperatively, postoperative Inotrope Score and drug complications where P<0.001. Conclusions: prophylactic of either amiodarone or magnesium sulfate are safe and relatively effective in preventing early postoperative arrhythmia in children after corrective heart surgery for CHD.