Background and Objective: Endoscopic or percutaneous biliary drainage with self-expandable metallic stents (SEMS) is widely used for the palliation of cholestasis in patients with advanced hilar cholangiocarcinoma. However, little is known about which is the better option in patients with advanced hilar cholangiocarcinoma. We compared the clinical outcomes of these 2 methods of biliary decompression in these patients. Design and Setting: Multicenter retrospective study. Patients: A total of 85 patients with newly diagnosed advanced hilar cholangiocarcinoma (Bismuth III or Bismuth IV) and who did not receive an operation, chemotherapy, or radiotherapy were retrospectively reviewed. Forty-four of the 85 received endoscopic SEMS and 41 received percutaneous SEMS. Interventions: Endoscopic SEMS or percutaneous SEMS. Main Outcome Measurements and Results: Baseline characteristics were similar in the 2 groups, but the rate of successful biliary decompression was significantly higher in the percutaneous SEMS group than in the endoscopic SEMS group (92.7% vs 77.3%, respectively, P = .049). Overall rates of procedure-related complications were similar for the 2 groups, but 1 death (from biliary sepsis) occurred in the endoscopic SEMS group. Median survival of patients in whom biliary drainage was successful initially, regardless of which procedure was performed, was much longer than that of patients who had failed biliary drainage (8.7 months vs 1.8 months, respectively, P < .001). Once successful biliary decompression had been achieved, median survival and stent patency duration were similar in the 2 study groups. Limitation: Retrospective study. Conclusions: Percutaneous SEMS may be chosen for initial biliary drainage in patients with advanced type III or IV hilar cholangiocarcinoma, given higher initial success rate and low level of procedure-related cholangitis.