Background A single session of EUS-guided biliary drainage (EUS-BD) may be a viable alternative to ERCP in patients with malignant distal common bile duct (CBD) obstruction. There is no study comparing EUS-BD and ERCP for the relief of distal malignant biliary obstruction. Objective To compare the outcomes of self-expandable metal stent (SEMS) placement for malignant distal biliary obstruction by using ERCP and EUS-BD. Study Design Multicenter, retrospective analysis. Setting Tertiary referral centers. Patients Patients with malignant distal CBD obstruction requiring SEMS placement. Interventions Patients in the EUS-BD group underwent EUS-guided choledochoduodenostomy (EUS-CDS) or EUS-guided antegrade (EUS-AG) procedures after 1 or more failed ERCP attempts. Patients in the ERCP group underwent retrograde SEMS placement. Main Outcome Measurements Composite success (the ability to complete the intended therapeutic procedure in a single session and resulting in a greater than 50% decrease in bilirubin over 2 weeks). Results The study included 208 patients, 104 treated with ERCP and 104 treated with EUS-BD (68 EUS-CDS, 36 EUS-AG). SEMS placement was successful in 98 patients in the ERCP group and 97 in the EUS-BD group (94.23% vs 93.26%, P  = 1.00). The frequency of adverse events in the ERCP and EUS-BD groups was 8.65% and 8.65%, respectively. Postprocedure pancreatitis rates were higher in the ERCP group (4.8% vs 0, P  = .059). The mean procedure times in the ERCP and EUS-BD groups were similar (30.10 and 35.95 minutes, P  = .05). Limitations Retrospective analysis. Conclusions In patients with malignant distal CBD obstruction requiring SEMS placement, the short-term outcome of EUS-BD is comparable to that of ERCP.