Background-There is increasing evidence that cardiopulmonary bypass (CPB) may be responsible for the morbidity associated with coronary artery bypass grafting (CABG) surgery. Recent developments in cardiac stabilization devices have made CABG without CPB feasible. However, there is conflicting evidence to date from published trials comparing outcomes between CABG performed with and without CPB, with some trials indicating an advantage to the avoidance of CPB and others showing little benefit. Methods and Results-In a single-center randomized trial, 300 patients requiring CABG surgery at a single institution were prospectively randomized to have the procedure performed with CPB (nϭ150) or on the beating heart (nϭ150). Exclusion criteria for the trial included emergency procedure, concomitant major cardiac procedures, ejection fraction Ͻ30%, and reoperation. In-hospital outcomes were analyzed on an intention-to-treat basis. A mean of 3.0Ϯ0.9 grafts were performed in the CPB group compared with 2.8Ϯ0.9 grafts in the beating-heart group (Pϭ0.06). There were no significant differences between the CPB group and the beating-heart group in mortality (0.7% versus 1.3%; Pϭ1.0), transfusion (8.7% versus 9.3%), perioperative myocardial infarction (0.7% versus 2.7%; Pϭ0.37), permanent stroke (0% versus 1.3%; Pϭ0.50), new atrial fibrillation (32% versus 25%; Pϭ0.20), and deep sternal wound infection (0.7% versus 0%; Pϭ1.0). The mean time to extubation was 4 hours, the mean stay in the intensive care unit was 22 hours, and the median length of hospitalization was 5 days in both groups (PϭNS). Conclusions-In