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Background: Endoscopic biliary stenting is a well-established palliative treatment in patients with unresectable malignant biliary strictures. Obstruction of uncovered self-expanding metal stent (SEMS) due to tumor ingrowth is the most frequent complication. Partially covered SEMS might increase stent patency but could favor complications related to stent covering, such as pancreatitis, cholecystitis, and migration. The aim of this study was to evaluate the efficacy and safety of partially covered SEMS in patients with an unresectable malignant biliary stricture. Methods: Patients with malignant extrahepatic biliary obstruction treated endoscopically with partially covered SEMS were included in this multicenter, prospective, nonrandomized study. Results: One hundred ninety-nine patients were endoscopically treated with partially covered SEMS in 32 Spanish hospitals. Clinical success after deep cannulation was 96%. Early complications occurred in 4% (3 pancreatitis, 2 cholangitis, 1 hemorrhage, 1 perforation, and 1 cholecystitis). Late complications occurred in 19.5% (18 obstructions, 10 migrations, 6 cholangitis without obstruction, 3 acute cholecystitis, and 2 pancreatitis), with no tumor ingrowth in any case. Median stent patency was 138.9 ± 112.6 days. One-year actuarial probability of stent patency was 70% and that of nonmigration was 86%. Multivariate analysis showed adjuvant radio- or chemotherapy as the only independent predictive factor of stent patency and previous insertion of a biliary stent was the only predictive factor of migration. Conclusions: The partially covered SEMS was easily inserted, had a high clinical success rate, and prevented tumor ingrowth. The incidence of possible complications related to stent coverage, namely, migration, pancreatitis, and cholecystitis, was lower than in previously published series. [ABSTRACT FROM AUTHOR]