Background: Cardiac surgeries use 10%–15% of red blood cells transfused in the United States, despite benefits of limiting transfusions. We sought to evaluate the the feasibility and impact of a restrictive transfusion protocol on blood use and clinical outcomes in patients undergoing isolated primary coronary artery bypass grafting (CABG). Methods: Blood conservation measures, instituted in 2012, include preoperative optimization, intraoperative anesthesia and pump fluid restriction with retrograde autologous priming and vacuum-assisted drainage, use of aminocaproic acid and cell saver, intra- and postoperative permissive anemia, and administration of iron and lowdose vasopressors if needed. Medical records of patients who underwent isolated primary CABG from 2009–2012 (group A; n=375) and 2013–2016 (group B; n=322) were compared. Results: CABG with grafting to 3 or 4 coronary arteries was performed in 262 (70%) and 222 (69%) patients and bilateral internal thoracic artery grafting in 202 (54%) and 196 (61%) patients in groups A and B, respectively. Mean preoperative and intraoperative hematocrit was 40.3% and 40.7%, 28.9% and 29.4% in groups A and B, respectively. Total blood transfusion was 24% and 6.5%, intraoperative transfusion 10% and 1.2%, postoperative transfusion 19% and 5.3% (p<0.0001 for all) in groups A and B, respectively. Median postoperative length of stay was 5.0 days in group A and 4.5 days in group B (p =.02), with no significant differences between groups in mortality or morbidity. Conclusions: A restrictive transfusion protocol reduced blood transfusions and postoperative length of stay without adversely affecting outcomes following isolated primary CABG.