Concern about the safety of the allogeneic blood supply has made preoperative autologous blood donation (PAD) routine before major noncardiac operations. However, the costs and benefits of PAD in elective coronary artery bypass grafting (CABG) are not well established. We used decision analysis to (1) calculate the cost-effectiveness of PAD in CABG, expressed as cost per year of life saved, and (2) compare the health benefits of reducing allogeneic transfusions with the potential risks of autologous blood donation by patients with coronary artery disease. A prospective study of 18 institutions provided data on transfusion practice and blood product costs in CABG. On average, PAD in CABG costs $508,000 to $909,000 per quality-adjusted year of life saved, depending on the number of units donated. Preoperative autologous blood donation is more cost-effective (as low as $518,000 per year of life saved) when targeted to younger patients undergoing CABG at centers with high transfusion rates. The cost-effectiveness of PAD is strongly dependent on estimates of posttransfusion hepatitis incidence, but less so on plausible estimates of the current risk of human immunodeficiency virus transmission. Although the actual risk of PAD is uncertain, even a small fatality risk (> 1 per 101,000 donations) associated with blood donation by patients awaiting CABG negates all life expectancy benefits of PAD. At current costs, PAD by patients awaiting CABG is not cost-effective, producing small health benefits at high societal cost. For the individual patient, the risk of donating blood before CABG may well outweigh the benefits associated with fewer allogeneic transfusions.