ERCP-guided stent implantation into the bile or pancreatic duct is considered an established treatment for obstructions. However, there are cases with not introducible catheter into the papilla or not reachable papilla because of both pyloric/duodenal stenosis or previous GI surgery.The aim of the study was to investigate feasibility & outcome of the EUS-guided translumenal drainage of the i) bile duct in cases with failure of PTCD or in patients who decline it & ii) pancreatic duct.Methods: All consecutive patients were enrolled in this ongoing prospective observational unicenter study (case series) through a 6-year time period. Patient- & intervention-related specifics were documented. Feasibility was characterized by success rate (e.g., regressive cholestasis, improval of clinical symptoms) & outcome by complication rate (frequency of bleeding or perforation), mortality & short-term follow-up.Results: From 2002-2008, 67 patients underwent endoscopic interventions (n=78) for translumenal drainage into the i) bile duct (main indication, cholestasis because of advanced tumor growth), n=32 (47.8%; interventions, n=33); ii) pancreatic duct (chronic pancreatitis), n=35 (52.2%; interventions, n=45). After translumenal ductal puncture, cholangio- & pancreaticography were successful in each case (100%). While cholangiodrainage was achieved in 25/32 subjects (technical success rate, 78%; plastic prosthesis, n=6; metallic stent, n=19), drain into the pancreatic duct was placed in 21/35 individuals (60%; not required, n=1) using this novel translumenal route: Transgastric drainage, n=7/35 (20%); transpapillary drainage with ERCP-based rendesvouz, n=14/35 (40%). Though slight postinterventional pain was observed in each case, only cholangitis (n=3/33; 9.1%) & hemobilia (n=1/33; 3%) occurred after cholangiodrainage (major complication, n=1 resulting in mortality of 3%) whereas after translumenal drainage of the pancreatic duct, bleeding (n=3/45; 6.7%), perforation (n=1/45; 2.2%), pancreatitis (n=2/45; 4.4%) & pseudocysts (n=4/45; 8.9% - no deaths but following surgery, n=9) were documented resulting in a periinterventional morbidity of 15.2% (n=5/33) & 22.2% (n=10/45), resp. Endoscopic reintervention rate was 21.2% (n=7/33) & 17.8% (n=8/45), resp. (main cause, stent dislocation).Conclusion: In selected patients, EUS-guided translumenal drainage of the bile & pancreatic duct is a reasonable, feasible & promizing endoscopic approach, with an acceptable periinterventional risk. It broadens the spectrum of therapeutic options but still needs further evaluation on the indication & the advantageous impact as well as long-term follow-up investigation.