Biliary strictures after liver transplantation are a therapeutic challenge for endoscopy. Anastomotic strictures occur in 10% of patients after liver transplantation, leading untreated to mortality and ultimately to graft failure. Despite of successful reports, to date, there is no defined endoscopic therapy regimen for these cases. Therefore the aim of this study was to determine the most suitable concept for endoscopic treatment of post-liver transplant anastomotic strictures (PTAS). A total of 72 patients post-liver transplantation, who received endoscopic retrograde cholangiography (ERC) as a consequence of suspected biliary complications were retrospectively screened for the presence of PTAS. In all patients graft rejection or bile duct ischemia were excluded prior to ERC by liver biopsy or Doppler ultrasound respectively. We compared either balloon dilatation (BD) alone or dilatation plus placement of an increasing number of bile duct endoprostheses (BD + endoprostheses) in a retrospective analysis. A total of 25 of 75 patients showed PTAS. Overall, endoscopic therapy was successful in 22 of 25 patients (88%). BD was initially successful in 89% but showed recurrence in 62%. BD + endoprostheses was initially successful in 87%, and recurrence was observed only in 31%. All recurrences were successfully retreated by BD + endoprostheses. During 22 of 109 (20%) treatment sessions stone extraction was necessary. Complication rate was low with bacterial cholangitis in 8 of 109 (7.3%) sessions, mild pancreatitis in 10 of 109 (9%) sessions and minor bleeding in 2 of 25 (8%) sphincterotomies. Median follow-up after conclusion of endoscopic therapy is 6 months (range 1-43). In conclusion, our data confirm that endoscopic therapy of PTAS is highly effective and safe. As primarily successful BD shows a high rate of recurrence, we recommend a combination of BD followed by an increasing number and diameter of endoprostheses. Therapy sessions are effective at short intervals of every 2-3 months.