ABSTRACT Objective To evaluate the practical application of ultrasound guided percutaneous transhepatic cholangiography drainage（PTCD） combined with endoscopic cholangiopancreatography（ERCP） in patients with difficult ERCP.Methods From October 2020 to December 2022，ultrasound-guided PTCD combined with ERCP was performed in patients who had difficult or failed conventional ERCP treatment.The diagnostic and therapeutic procedures of ERCP were successfully completed. The blood white blood cells, bilirubin, transaminases, and amylase between pre- and 2 days post PTCD-ERCP combination were analyzed.Results The present study included 17 patients with difficult ERCP，including 3 cases of extrahepatic bile duct stones，7 cases of ampullary carcinoma，4 cases of pancreatic head cancer，1 case of biliary anastomotic stricture and calculus，2 cases of bile duct stricture post liver transplantation，PTCD-ERCP combination was successfully performed in each patient.Patients with common bile duct stones underwent endoscopic stone removal and nasobiliary drainage，while those with biliary obstruction underwent biliary dilation and stent placement.The clinical symptoms and laboratory indicators of all 17 patients improved significantly after the procedure，and no severe complications occurred.Ultrasound-guided PTCD combined with ERCP can improve the success rate of ERCP operation，and is suitable for minimally invasive management of biliary diseases in some patients with liver transplantation and rerouting of gastrointestinal tract.Conclusion Ultrasound-guided PTCD combined with ERCP is a highly successful and safe procedure with broad clinical utility.