Background/Aims: To prospectively evaluate our palliative management of unresectable cholangiocarcinoma (CC) treated with tailored multimodal oncological therapy. Methods: Between January 2005 and January 2010, 50 consecutive patients with unresectable CC and jaundice were palliated with percutaneous drainage. Forty-three patients underwent metallic-stent implantation followed by brachytherapy. Patients were divided into two arms: the intra-arterial chemotherapy arm (IA arm, n=17) consisted of patients treated with locoregional treatment (IA admission of Cisplatin and 5-fluorouracil, or chemoembolization with Lipiodol) and/or systemic chemotherapy, while the systemic chemotherapy arm (IV arm, n=23) included all the other patients, who were treated only with systemic chemotherapy. Results: In total, 78 metal self-expandable stents were placed. Hilar involvement with mass-forming and periductal infiltrating types of CC (84%) was predominant. The average number of percutaneous interventional procedures was 11.61 per patient (range, 4-35). The median overall survival from diagnosis of disease for all patients was 13.5 months (range, 11.0-18.8 months). The median overall survival times were 25.2 months (range, 15.2-31.3 months) and 11.5 months (range, 8.5-12.6 months) in the IA and IV arms, respectively (p<0.05). The 1-, 2-, and 3-year survival rates in the IA and IV arms were 88.2%, 52.9%, and 10.1% and 43.5%, 25.4, and 0%, respectively. There were no major complications (WHO III/IV) due to interventional procedures. Conclusions: We could reach acceptable prognosis in patients with unresectable CC using complex tailored oncological therapy. However, the main limitations of prolonging survival are performance status, patient compliance and the maintaining of biliary tract patency. (Gut Liver 2010;4(Suppl. 1):S82-88)