Background-: Despite its widespread use and short-term efficacy, substantial uncertainty remains about the long-term outcomes and cost-effectiveness of off-pump coronary artery bypass (OPCAB). Methods and results-: A retrospective review of prospectively collected data was conducted of 6665 consecutive patients undergoing isolated coronary artery bypass graft (CABG) at our institution during 1999 to 2006. All patients were followed up until September 30, 2008. Short-and long-term outcomes were compared between OPCAB and conventional CABG. The 2 main long-term outcome measures were repeat revascularization and the composite outcome of major vascular events. Cost comparison at 2 years in a propensity-matched sample during follow-up was also a study interest. The overall mean baseline age was 60.3±8.6 years, and 17.0% were women. Compared with conventional CABG, patients who underwent OPCAB had lower rates of atrial fibrillation (P=0.003) and requirements for blood transfusion (P=0.03) and ventilation time >24 hours (P<0.001). After an average of 4.5 years of follow-up, the rates of repeat revascularization (adjusted hazard ratio, 1.40; 95% confidence interval, 1.03 to 1.89) and major vascular events (adjusted hazard ratio, 1.23; 95% confidence interval, 1.09 to 1.39) were significantly higher in the OPCAB than the conventional CABG group. At 2 years, OPCAB was associated with increased additional direct costs per patient compared with conventional CABG and had a similar survival rate. Conclusions-: Compared with conventional CABG, OPCAB is associated with small short-term gain but increased long-term risks of repeat revascularization and major vascular events, especially among high-risk patients. Moreover, OPCAB consumes more resources and is less cost-effective in the long run. Copyright © 2010 American Heart Association. All rights reserved.