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Background: To evaluate whether postoperative administration of intravenous low-dose amiodarone and magnesium sulfate (MgSO(4)) combination would reduce the incidence of atrial fibrillation following coronary artery bypass grafting (CABG) in normomagnesemic high-risk patients for postoperative atrial fibrillation (POAF)., Methods: A total of 136 patients undergoing elective CABG and had > or =3 risk factors for POAF were prospectively randomized to one of three groups, to receive a single dose of amiodarone (5 mg/kg) and MgSO(4) (1.5 g) (combination group, n = 44), or an equal dose of amiodarone (amiodarone group, n = 44) or equal volumes of saline (control group, n = 48) at early postoperative period. Continuous electrocardiographic (ECG) monitoring was performed for the first 48 hours and an ECG was recorded every 8 hours later. POAF longer than 30 minutes or for any length requiring treatment, and the drug-related side effects were recorded., Results: The study population showed a homogeneous distribution regarding risk factors for POAF and there was no significant difference in patient characteristics, echocardiographic variables, or operative variables among three groups. POAF developed in 4 patients in combination group, in 16 patients in amiodarone group and in 16 patients in control group, representing a 24% relative risk reduction between the combination group and control group (p = 0.023). No statistically significant difference regarding incidence of POAF was observed between amiodarone and control groups., Conclusions: Combined prophylactic therapy with amiodarone and MgSO(4) at the early postoperative period without a maintenance phase is an effective, simple, well-tolerated, and possibly cost-effective regimen to prevent POAF in normomagnesemic, high-risk patients.