Although morbidity and mortality after liver resection have improved over the last two decades, complex liver resections still require perioperative blood transfusions. In this report, we describe the use of a combined left trisegmentectomy and caudate lobectomy, along with resection of the inferior vena cava, to treat a large intrahepatic cholangiocarcinoma in a Jehovah's Witness. To our knowledge, this is the first report of major liver resection for a large malignant tumor in this patient population. We also discuss the perioperative strategy and surgical technique we used to minimize blood loss and avoid transfusion. This approach could be a safe alternative for use in all patients with complex liver tumor, regardless of their religious beliefs, to reduce the risks and cost associated with blood transfusion.