We aimed to quantify the effect of avoiding cardiopulmonary bypass on outcomes in high-risk patients. Of the 2079 consecutive CABG's performed by three surgeons between April 1997 and September 2002, 389 were classified as high-risk according to the European System for Cardiac Operative Risk Evaluation (EuroSCORE) risk stratification, with a score of >5. The off-pump group had 196 patients and the on-pump group had 193 patients. Multivariate logistic regression was used to assess the effect of off-pump on in-hospital outcomes, while adjusting for treatment selection bias with a propensity score. The incidence of hypertension, hypercholesterolaemia, and renal dysfunction were higher in the off-pump group. The median EuroSCORE for off-pump patients was 7 (6-8), while for the on-pump patients was 7 (6-8; P=0.31). After adjusting for the propensity score, off-pump patients were less likely to have stroke (OR 0.17; P=0.041), renal failure (OR 0.35; P=0.029), blood transfusion (OR 0.12; P<0.001), prolonged mechanical ventilation (OR 0.36; P=0.021), and inotrope support (OR 0.35; P<0.001). Off-pump patients also had significantly shorter post-operative hospital stays. There was no significant difference between off-pump and on-pump patients in terms of in-hospital and mid-term mortality. Off-pump CABG is justified in EuroSCORE high-risk cases.