Cholangiocarcinoma is an aggressive malignancy with 5-year survival rates<15%. Selected patients present with localized but unresectable disease and are candidates for orthotopic liver transplantation (OLT). The purpose of this study was to evaluate a multi-institutional experience with liver transplantation for this malignancy. Two hundred eighty patients with cholangiocarcinoma treated with OLT from 1987 to 2005 were identified in The United Network for Organ Sharing database. Patient and allograft survivals were calculated and the potential prognostic value of multiple clinicopathologic variables was assessed. At a median follow-up interval of 452 days (range: 0-6,166 days), 1- and 5-year patient survivals were 74 and 38%, respectively, with 49 actual 5-year survivors and 21 actual 10-year survivors. Posttransplant 1- and 5-year allograft survivals were 69 and 36%, respectively. Study variables associated with improved survivals included diagnosis of cholangiocarcinoma pre-OLT [5-year overall survival (OS): 68 vs. 20% for patients with incidental diagnoses at the time of OLT, p<0.001] and OLT after 1993 (5-year OS: 45 vs. 30% pre-1994, p<0.01). In contrast, the diagnosis of concomitant primary sclerosing cholangitis did not impact survivals (5-year OS: 41 vs. 50% without primary sclerosing cholangitis, p=0.402). Selected cholangiocarcinoma patients treated with OLT experience a survival benefit. Diagnosis of cancer prior to OLT allows for better staging and pre-OLT therapy that may translate into improved outcomes. These data support the continued development of multimodality cholangiocarcinoma treatment protocols that include OLT.