Jehovah's Witnesses who require operation represent a challenge to the physician because of the patients' refusal to accept blood transfusion. We report a 20-year experience with a consecutive series of 542 Jehovah's Witness patients ranging in age from 1 day to 89 years who underwent operation. Early mortality (within 30 days after operation) was 9.4%. In 362 patients requiring temporary cardiopulmonary bypass, early mortality was 10.7%. Mortality was 13.5% among 126 patients who had single- or double-valve replacement. The only deaths among patients who had aortic valve replacement or repair of a ventricular septal defect occurred in those who had some serious complication before operation. Preoperative or postoperative anemia was a contributing factor in 12 deaths, and loss of blood was the direct cause of three deaths. Cardiovascular operations can be performed safely without blood transfusion.