This article explores the major challenges and specialized strategies involved in managing cardiovascular surgery patients who are Jehovah’s Witnesses and refuse blood transfusions due to their religious beliefs. It delves into preoperative, intraoperative, and postoperative approaches aimed at minimizing blood loss and optimizing patient outcomes while respecting their autonomy. Preoperative measures focus on correcting anemia and coagulopathy through targeted interventions, such as iron supplementation and erythropoietin therapy, and meticulous screening for bleeding disorders. Intraoperative techniques include the use of vasoconstrictors, hemostatic agents, and innovative blood conservation methods like acute normovolemic hemodilution and cell salvage. Postoperative care emphasizes infection control, hemostasis, and judicious monitoring to prevent anemia and facilitate recovery. Through a multidisciplinary approach and adherence to evidence-based practices, healthcare providers can effectively meet the needs of Jehovah’s Witness patients, ensuring safe and successful cardiovascular surgery outcomes without the use of blood transfusions.