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Results of liver transplantation in the treatment of cholangiocarcinoma have been poor as a result of the high incidence of locoregional dissemination and tumor recurrence. This study evaluates the effect of neoadjuvant chemoradiation therapy combined with orthotopic liver transplantation in a carefully selected group of patients with hilar cholangiocarcinoma.Seventeen patients were included in the study. The neoadjuvant protocol included 6000 cgy biliary brachytherapy delivered through percutaneous transhepatic catheters and intravenous infusion of 5-fluorouracil (300 mg/m2/day) until transplantation.Five of the 17 patients demonstrated tumor progression precluding transplantation. One patient died of sepsis on the waiting list. Eleven patients underwent liver transplantation, a median of 3.4 months (range = 1–26 months) after diagnosis. Five of the 11 (45%) are alive without evidence of tumor recurrence with a median follow up of 7.5 years (range = 2.8–14.5 years). Six deaths occurred in the transplanted patients. Tumor recurrence was responsible for two deaths at 10 and 18 months, respectively, after transplantation. Three mortalities resulted from bacterial or fungal peritonitis and sepsis. One patient underwent re-transplantation for chronic rejection and died from graft failure resulting from hepatic artery thrombosis 16 months after diagnosis without evidence of tumor recurrence. Complications of transhepatic catheter placement included bile duct perforation (n = 4) and biliary-portal vein fistula (n = 1). All these patients died of tumor recurrence or sepsis.Cholangiocarcinoma should not be considered an absolute exclusion criteria for orthotopic liver transplantation. Long-term, tumor-free survival was achieved in 45% of the transplanted patients. Complications of biliary catheter placement for brachytherapy were associated with poor outcome.