Ventricular fibrillation during reperfusion after aortic cross-clamping for coronary artery bypass grafting may cause subendocardial injury. We investigated the use of lidocaine to prevent ventricular fibrillation during this period. In a blind, prospective, randomized trial, 91 consecutive patients undergoing elective coronary artery bypass graft procedures were given lidocaine (2 mg/kg) or normal saline immediately before removal of the aortic cross-clamp. The groups were similar with respect to demographic, clinical, and intraoperative variables. Myocardial preservation techniques were similar in both groups. Of 47 patients receiving lidocaine, 38 recovered a supraventricular rhythm without ventricular fibrillation, compared with only 5 of 44 patients in the control group (p less than .001). When ventricular fibrillation occurred, patients in the control group required a greater number of direct-current countershocks (2.31 versus 1.86) to convert to sinus rhythm. Transient heart block, requiring temporary pacing, developed in 3 patients in the lidocaine group, compared with 1 patient in the control group. There was no significant difference between the groups in the requirement for perioperative inotropic support (6 of 47 versus 6 of 44) or the number of myocardial infarctions (2 of 47 versus 1 of 44), and there were no deaths in either group. Lidocaine infusion immediately before removal of the aortic cross-clamp significantly reduces the incidence of ventricular fibrillation during the reperfusion period after cardiopulmonary bypass.