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Background: Atrial fibrillation (AF) is a common complication reported in 20% to 40% of patients after coronary operations. Sotalol alone and magnesium alone have been shown to partially decrease the incidence of AF. The goal of this study was to evaluate the efficacy of these two pharmacological agents, used alone or in combination, to reduce postoperative AF., Methods: Two hundred seven consecutive coronary artery bypass patients (mean age 62 +/- 11 years) were randomized to receive sotalol alone (80 mg twice daily for 5 days starting from the morning of the first postoperative day) (group S), magnesium alone (1.5 g daily for 6 days starting in the operating room just before cardiopulmonary bypass) (group M), both pharmacologic agents at the same dosages (group S+M), or no antiarrhythmic agents (group CTR). All patients with an ejection fraction less than 0.40 were excluded., Results: The incidence of postoperative AF was 11.8% (6/51) in the S group, 14.8% (8/54) in the M group, 1.9% (1/52) in the S+M group, and 38% (19/50) in the CTR group. The following differences were significant: group CTR versus groups S, M, and S+M with values of p = 0.002, p = 0.007 and p < 0.0001, respectively; and group S+M versus groups S and M with p = 0.04 and p = 0.01, respectively., Conclusions: Incidence of AF after coronary operation was significantly reduced by the administration of sotalol alone and magnesium alone; more importantly, the incidence was further reduced by combining these agents.