INTRODUCTION: Endoscopic ultrasound-guided (EUS) biliary drainage was used as an alternative method for patients who failed endoscopic retrograde cholangiopancreatography (ERCP). In recent years, an increasing number of patients was treated with EUS-biliary drainage (BD), but lack of data was available to value the efficacy and safety between EUS and ERCP. Therefore, a review was needed to evaluate the similarities and differences between the two methods and explored whether EUS-guided biliary drainage could be considered as first-line treatment. EVIDENCE ACQUISITION: We searched the Pubmed/Medline, Embase, Web of science, Google scholar, the Cochrane Library and Clinical trials of electronic databases till October 2018 for all English language. Primary outcomes to comparison included technical success, clinical success and adverse events. Secondary outcomes consisted of stent dysfunction requiring reintervention and procedure duration, Data from selected studies were collected to calculate the odds ratios (OR) and standard mean difference (SMD). EVIDENCE SINTHESIS: We searched 469 studies and at last identified 4 eligible trials. These included a total of 428 patients, 215 in the EUS group and 213 in the ERCP group. There was no difference in technical success (OR, 0.95; 95% CI: 0.45-2.02; I-2=0%), clinical success (OR, 0.87; 95% CI: 0.42-1.79; I-2=0%) and adverse events between 2 procedures (OR, 0.76; 95% CI: 0.29-2.00; I-2=55%) but EUS-BD consisted of lower rate of reintervention (OR, 0.30; 95% CI: 0.14-0.63; I-2=0%),and fewer procedure-related adverse events in pancreatitis and cholangitis (OR, 0.14; 95% CI: 0.04-0.51; I-2=0%). There was no difference in length of procedure duration, with a pooled standard mean difference of 0.26 (95% CI: -0.15 to 0.66). CONCLUSIONS: EUS-BD and ERCP-BD in terms of relief of malignant biliary obstruction presented the similarity rate of technical success, clinical success and there is no significant difference in adverse events of two procedures. EUS-BD could be used as a substitute for ERCP-BD, even considered as first-line treatment.