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Background and study aims Endoscopic retrograde cholangiography (ERC) in patients with complex surgically-altered anatomy (SAA) is technically demanding and has limitations. Developments in EUS-guided procedures allow alternative approaches for patients with altered gastrointestinal anatomy and biliary lithiasis. Patients and methods Single-center, retrospective review of prospectively entered patients with SAA who underwent EUS-guided hepaticogastrostomy (HGS) followed by an interval antegrade endoscopic clearance of biliary lithiasis. Results 9 patients with Roux-en-Y anatomy underwent HGS to allow clearance of biliary lithiasis after a mean of 2.5 procedures. Technical success was achieved in 100 % of patients utilizing subsequent antegrade endoscopic techniques after HGS including: balloon sweep (9), transpapillary balloon dilation (8), cholangioscopy with electrohydraulic lithotripsy (4), and mechanical lithotripsy (1). HGS stents were removed in all patients. 1 adverse event (cholangitis) occurred after cholangioscopy and prolonged intraductal electrohydraulic lithotripsy. Conclusion EUS-guided antegrade therapy for the management of biliary lithiasis in patients with altered gastrointestinal anatomy appears efficacious with a low risk of adverse events. These preliminary results suggest this approach should be considered at centers with available expertise.