Background-:Off-pump coronary artery bypass grafting compared with coronary revascularization with cardiopulmonary bypass seems safe and results in about the same outcome in low-risk patients. Observational studies indicate that off-pump surgery may provide more benefit in high-risk patients. Our objective was to compare 30-day outcomes in high-risk patients randomized to coronary artery bypass grafting without or with cardiopulmonary bypass. Methods and Results-: We randomly assigned 341 patients with a EuroSCORE ≥5 and 3-vessel coronary disease to undergo coronary artery bypass grafting without or with cardiopulmonary bypass. Patients were followed through the Danish National Patient Registry. The primary outcome was a composite of adverse cardiac and cerebrovascular events (ie, all-cause mortality, acute myocardial infarction, cardiac arrest with successful resuscitation, low cardiac output syndrome/cardiogenic shock, stroke, and coronary reintervention). An independent adjudication committee blinded to treatment allocation assessed the outcomes. Baseline characteristics were well balanced between groups. The mean number of grafts per patient did not differ significantly between groups (3.22 in off-pump group and 3.34 in on-pump group; P=0.11). Fewer grafts were performed to the lateral part of the left ventricle territory during off-pump surgery (0.97 versus 1.14 after on-pump surgery; P=0.01). No significant differences in the composite primary outcome (15% versus 17%; P=0.48) or the individual components were found at 30-day follow-up. Conclusions-: Both off-and on-pump coronary artery bypass grafting can be performed in high-risk patients with low short-term complications.