Objective: To study the therapeutic effect of Endoscopic ultrasound-guided biliary drainage (EUS-BD) with a nitinol fully covered self-expandable metal stent in patients with malignant obstructive jaundice when endoscopic retrograde cholangiopancreatography (ERCP) fails. Methods: From January 2016 January 2018, all patients with malignant obstructive jaundice during hospitalization underwent EUS-guided biliary drainage with a nitinol fully covered self-expandable metal stent, and the operation success rate, the clinical success rate, complications, length of hospital stay and survival time were observed. Results: Of 36 patients, 34 cases had successful operation; the operation success rate was 94.44% (34/36). The clinical success rate was 88.89% (32/36). Hemobilia occurred in 1, acute cholangitis in 1, and bile peritonitis in 1; improved after conservative treatment, the complication rate is 8.33% (3/36). Hospital stay and survival time was 21.54 ± 4.73 days and 220.54 ± 54.76 days, respectively. Conclusion: EUS-BD with a nitinol fully covered self-expandable metal stent may be a feasible and effective treatment option in patients with malignant biliary obstruction when ERCP fails.