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Aims: In cases of malignant distal biliary obstruction, ERCP is the preferred technique for bile duct drainage. In case of failure, the alternative techniques are percutaneous transhepatic biliary drainage (PTBD) and more recently endoscopic ultrasound-guided biliary drainage. A new type of stent called the electrocautery-enhanced lumen-apposing metal stent (EC-LAMS) has been developed to enable the performance of biliary-enteric anastomosis under EUS-guidance in a single step, without prior bile duct puncture or the need for a guidewire. The aim of our study was to compare the real-life efficacies of PTBD and EUS-BD with the EC-LAMS for cases of ERCP failure in patients with malignant biliary obstruction. Methods: We performed a monocentric retrospective study comparing PTBD and EUS-BD with the use of electrocautery-enhanced lumen-apposing metal stent in the context of a malignant distal biliary obstruction after ERCP failure. Results: 95 patients were included (50 in EUS-BD group and 45 in PTBD group). The main etiology of malignant obstruction was adenocarcinoma of the head of pancreas (85%). There was a significant difference in favor of endoscopic ultrasound-guided biliary drainage using electrocautery-enhanced lumen-apposing metal stent for the following criteria: clinical success: 89.3% vs. 45.5%; p < 0.0001; procedure-related adverse event rate: 2.12% vs. 22.7%; p = 0.003; duration of post-drainage hospitalization: 3.5 vs. 8.2 days; p < 0.0001, overall survival (median survival): 118.2 vs. 42 days; p = 0.012, overall cost of the strategy per patient: 5098 vs. 9363 euros; p < 0.001. Conclusion: Our results are in favor of EUS-BD using electrocautery-enhanced lumen-apposing metal stent in case of ERCP failure for a distal tumor biliary obstruction. Operators performing ERCP for distal tumor biliary obstruction must learn this backup procedure because of its superiority over percutaneous transhepatic biliary drainage in terms of clinical success, safety, cost, and overall survival. [ABSTRACT FROM AUTHOR]