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The aim of this study is to compare the efficacy and safety of endoscopic ultrasonography guided biliary drainage and percutaneous transhepatic biliary drainage in the management of malignant obstructive jaundice after failed ERCP.We retrospectively analyzed the data of 66 consecutive patients with malignant obstructive jaundice admitted to our hospital between January 2014 and January 2016. Patients were performed endoscopic ultrasonography-guided biliary drainage in 36 cases (group A) and percutaneous transhepatic biliary drainage in 30 cases (group B) according to the results of the draw. Data on the following variables were compared between the 2 groups: the technical success rate, the clinical success rate, complications, length of hospital stay, and hospital costs.There was statistically significant difference in the clinical success rate (88.89% vs. 66.67%; χ2=4.84), complications (5.56% vs. 23.33%; χ2=4.39), length of hospital stay (11.54±3.73 d vs. 15.68±6.56 d; t=8.17) and hospital costs (23.52±8.44 thousand yuan vs. 32.81±6.06 thousand yuan; t=16.28) (P<0.05) between group A and group B. The technical success rate was higher in groups A than that in group B, although the difference did not reach statistical significance (94.44% vs. 86.67%; χ2=1.20; P>0.05).In the treatment of malignant obstructive jaundice, endoscopic ultrasonography guided biliary drainage is safer and more effective than percutaneous transhepatic biliary drainage when performed by experienced practitioners after failed ERCP. Its more widespread use is recommended.