The persistent variability in red blood cell transfusion practice in coronary artery bypass graft (CABG) patients, despite established guidelines, suggests inappropriate use. Our objective was to determine the impact of postoperative red blood cell (RBC) transfusion in entirely stable CABG patients. We investigated a cohort of 940 stable CABG patients from the 5,065 patients enrolled in the Multicenter Study of Perioperative Ischemia Epidemiology II (EPI II) Study with (1) low to moderate risk profile; (2) postoperative hemoglobin levels ≥ 10 g/dL; (3) minimal postoperative blood loss, and (4) no evidence of any morbid event on the day of surgery. RBC transfusion was assessed during the first 24 postoperative hours and multiorgan outcomes as well as markers of resource utilization from postoperative day one to hospital discharge. Transfused patients (N =190, 20.2 %) were more likely to suffer myocardial infarction (OR, 1.89; 95 % CI, 1.08 to 3.29; P = 0.02); renal dysfunction (OR, 3.35; 95 % CI, 1.01 to 11.1; P = 0.04); renal failure requiring dialysis (OR, 4.01; 95 % CI, 0.99 to 16.2; P = 0.05); and/or harvest site wound infection (OR, 5.45; 95 % CI, 1.87 to 15.9; P = 0.001). RBC transfusion was shown to be an independent predictor of composite morbidity outcome, cardiac morbidity, and harvest site wound infection in multivariate analysis. In transfused patients, the mean duration of hospitalization was increased by 2.5 days (14.4 days vs. 11.9 days; P < 0.001). In CABG patients with low to moderate mortality risk profiles, adequate hemoglobin values and low bleeding rates, postoperative RBC transfusion is associated with an increased risk for cardiac, renal and infectious morbidity, as well as increased health care expenses, without any detectable benefit.