OBJECTIVE Endoscopic ultrasound-guided hepaticogastrostomy (EUS-HGS) is an emerging alternative to percutaneous transhepatic biliary drainage (PTBD) in patients with a malignant biliary obstruction, in case of technical failure of endoscopic retrograde cholangiopancreatography (ERCP). However, this procedure is technically challenging, and dedicated stents have only recently become available. This study prospectively evaluated the safety and feasibility of EUS-HGS with a dedicated stent. METHODS This prospective single-center study included patients with inoperable malignant biliary obstruction that underwent an EUS-HGS. The primary outcome was safety. Technical and clinical success were evaluated as secondary endpoints. We used a partially covered self-expandable metal stent (pcSEMS) (30% uncovered and 70% covered) with anti-migration features. RESULTS EUS-HGS was attempted in 28 patients, achieving technical and clinical success rates of 89% (25/28) and 96% (22/23), respectively. Three patients (11%) experienced grade IIIA adverse events (AEs) (all cholangitis) within 30 days: two with undrained right-sided bile ducts requiring percutaneous drainage, and one patient due to blockage of a side branch at the level of the covered part of the stent for which an endoscopic stent exchange was successfully performed. Five patients died < 30 days due to disease progression, none of these patients experienced procedure-related AEs. Six out of the 22 patients with clinical success developed recurrent biliary obstruction after a median of 78 days (IQR 45-108). Obstruction was caused by hyperplasia at the uncovered portion of the stent (n = 3) and due to sludge obstructing the stent (n = 3). Successful re-intervention was performed in all patients. CONCLUSIONS This prospective study shows that EUS-HGS with a dedicated pcSEMS is feasible and safe. Tissue hyperplasia in the uncovered part of the stent and sludge obstruction may compromise long-term stent patency. Larger, comparative prospective studies are needed to assess optimal stent design and timing of EUS-HGS within the therapeutic algorithm.