Background: Cardiac surgery in Jehovah's Witnesses poses unique challenges. We have developed a comprehensive multimodality program for these patients and have obtained excellent results., Methods: Ninety-one Jehovah's Witness patients underwent cardiac surgery between 2000 and 2010. Preoperative, intraoperative, and postoperative considerations in the conduct of bloodless surgery in the Jehovah's Witness population are discussed. Mortality for isolated coronary artery bypass graft surgery and isolated aortic valve replacement was compared with predicted mortality from The Society of Thoracic Surgeons (STS) risk models. Perioperative outcomes were stratified by urgent and elective status of operations., Results: Mean age was 65±12.4 years. Comorbid conditions included hypertension (84.6%), diabetes mellitus (48.4%), previous myocardial infarction (23.1%), chronic lung disease (38.5%), peripheral vascular disease (20.9%), and renal failure (11%). In-hospital mortality was 5.5% (n=5). Mortality for isolated coronary artery bypass graft surgery and isolated aortic valve replacement was 2.2% (observed to expected ratio=1.05, 95% confidence interval: 0 to 3.02) and 5.6% (observed to expected=1.46, 95% confidence interval: 0 to 3.76), respectively. Other complications included reoperation (all=8.8%, cardiac=2.2%), sepsis (2.2%), sternal wound infection (1.1%), transient ischemic attack (1.1%), renal failure requiring dialysis (1.1%), and prolonged ventilation (18.7%). Major complication rates were not significantly different between the elective group and the urgent group., Conclusions: Bloodless cardiac surgery in Jehovah's Witness patients can be performed with excellent outcomes in both elective and urgent situations. Mortality rates for isolated coronary artery bypass graft surgery and isolated aortic valve replacement are within the expected 95% confidence intervals of STS predicted mortality., (Copyright © 2012 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)