To evaluate the effect of prophylactic procainamide on the frequency of postoperative atrial fibrillation in patients undergoing myocardial revascularization. Prospective, randomized, double-blind, placebo-controlled pilot study. Surgical intensive care unit and wards at a university hospital affiliate. A total of 46 patients undergoing myocardial revascularization. Twenty-two patients received procainamide (procainamide group) and 24 patients received placebo (control group). Procainamide was administered to the procainamide group within 1 hr of the patient's arrival in the intensive care unit and consisted of an intravenous loading dose (12 mg/kg) followed by a maintenance dose (2 mg/min) of procainamide. The control group received a similar volume of placebo. When the patient was able to take oral medication, the study drug was administered orally in a weight-adjusted dosage. Electrocardiograms (EKGs) were continuously monitored. Procainamide and N-acetyl procainamide serum concentrations were measured, and the dosages in the procainamide group were adjusted by an independent observer. The study drug was continued for 5 days or until an event occurred that resulted in dismissal from the study. The procainamide group and control group had similar preoperative demographic descriptors and operative variables, except for the mean left ventricular ejection fraction, which was lower in the control group than in the procainamide group (60% vs. 68%, p = .03 [Wilcoxon rank-sum test]). There were no hospital deaths. The number of episodes of postoperative atrial fibrillation was significantly reduced in the procainamide group (5 episodes in 129 patient days at risk [3.9%/day at risk]) compared with the control group (17 episodes in 161 patient days at risk [10.6%/day at risk], p = .04 [Fisher's exact test]). Complication rates were similar in both groups. In a pilot trial, prophylactic procainamide reduced the number of episodes of atrial fibrillation in patients after coronary artery bypass grafting. Procainamide also decreased the number of patients who experienced postoperative atrial fibrillation. However, due to the small sample size, this latter difference was not statistically significant. Further studies are needed to confirm this encouraging trend.