BACKGROUND Percutaneous transhepatic cholangiography is a diagnostic and therapeutic procedure that involves inserting a needle into the biliary tree, followed by the immediate insertion of a catheter. Endoscopic ultrasound-guided biliary drainage(EUS-BD) is a novel technique that allows BD by echoendoscopy and fluoroscopy using a stent from the biliary tree to the gastrointestinal tract.AIM To compare the technical aspects and outcomes of percutaneous transhepatic BD(PTBD) and EUS-BD.METHODS Different databases, including PubMed, Embase, clinicaltrials.gov, the Cochrane library, Scopus, and Google Scholar, were searched according to the guidelines for Preferred Reporting Items for Systematic reviews and Meta-Analyses to obtain studies comparing PTBD and EUS-BD.RESULTS Among the six studies that fulfilled the inclusion criteria, PTBD patients underwent significantly more reinterventions(4.9 vs 1.3), experienced more postprocedural pain(4.1 vs 1.9), and experienced more late adverse events(53.8%vs 6.6%) than EUS-BD patients. There was a significant reduction in the total bilirubin levels in both the groups(16.4-3.3 μmol/L and 17.2-3.8 μmol/L for EUSBD and PTBD, respectively; P = 0.002) at the 7-d follow-up. There were no significant differences observed in the complication rates between PTBD and EUSBD(3.3 vs 3.8). PTBD was associated with a higher adverse event rate than EUSBD in all the procedures, including reinterventions(80.4% vs 15.7%, respectively)and a higher index procedure(39.2% vs 18.2%, respectively).CONCLUSION The findings of this systematic review revealed that EUS-BD is linked with a higher rate of effective BD and a more manageable procedure-related adverse event profile than PTBD. These findings highlight the evidence for successful EUS-BD implementation.