Objective: To evaluate the efficacy of ex vivo hypothermic liver resection with caval preservation for irresectable Bismuth type IV hilar cholangiocarcinoma. Methods: The clinical records of two patients with Bismuth type IV hilar cholangiocarcinoma were reviewed. One of the two patients underwent in situ hypothermic extended right hepatectomy with of caval flow preservation, and the other one received complete ex vivo extended right liver resection with vena cava preservation. Results: The surgical duration of in situ hypothermic extended right hepatectomy lasted 14 h, and the intraoperative blood transfusion was 3 000 mL, however, the patient died due to multiple organ failure on the first day after surgery. The surgical procedure for ex vivo extended right liver resection took 15 h, and the blood transfusion requirement was 2 000 mL, with a cold ischemic time of 195 min, and a warm ischemic time of 20 min. This patient was discharged on postoperative day 30 with no occurrence of liver failure or other major complications, and was still alive with no evidence of vascular or biliary complications and no tumor recurrence or metastases during the 11-month follow-up period. Conclusion: Based on the premise of having wide experience in performing complex liver resection and living donation liver transplantation, the operation of ex vivo hypothermic extended right hepatectomy with caval preservation is safe, and it may be a therapeutic option for highly selected irresectable Bismuth type IV hilar cholangiocarcinoma.