Background: Only a few cases have been reported of EUS-guided drainage of obstructed pancreatic or bile ducts. An initial experience with EUS-guided rendezvous drainage after unsuccessful ERCP is reported. Methods: EUS-guided transgastric or transduodenal needle puncture and guidewire placement through obstructed pancreatic (n = 4) or bile (n = 2) ducts was attempted in 6 patients. Efforts were made to advance the guidewire antegrade across the papilla or surgical anastomosis. If guidewire passage was successful, rendezvous ERCP with stent placement was performed immediately afterward. Results: EUS-guided duct access and intraductal guide-wire placement was accomplished in 5 of 6 cases, with successful traversal of the obstruction, and rendezvous ERCP, with stent placement in 3 of 6 cases (two biliary, one pancreatic). The procedure was clinically effective in all successful cases (two patients with malignant obstructive jaundice, one with relapsing pancreatitis after pancreaticoduodenectomy). There was one minor complication (transient fever) but no pancreatitis or duct leak after successful or unsuccessful procedures. Conclusions: EUS is a feasible technique for allowing rendezvous drainage of obstructed biliary or pancreatic ducts through native papillae or anastomoses after initially unsuccessful ERCP.