Patients with unresectable, stage I and II perihilar cholangiocarcinoma were treated with neoadjuvant external beam irradiation, brachytherapy, and 5-fluorouracil and/or oral capecitabine prior to liver transplantation. Fifty-six patients underwent treatment between 1993 and 2003. Four patients died and 4 had disease progression prior to completion of neoadjuvant therapy. Forty-eight patients underwent operative staging and 14 had findings precluding transplantation. Twenty-eight patients underwent transplantation and 6 patients are awaiting transplantation. Three patients died from perioperative complications, and 4 developed recurrent disease 22 to 63 months after transplantation. Actuarial patient survival was 54% at 5 years for all 56 patients, 64% for 48 operatively staged patients, and 84% for 34 patients with negative staging operations. Actuarial survival was 88% at 1 year and 82 % 5 years after transplantation. Neoadjuvant chemoradiotherapy with liver transplantation achieves excellent results for patients with localized, regional lymph node negative, hilar cholangiocarcinoma.