The long-term results of liver transplantation for Budd-Chiari syndrome (BCS) and timely indication for the procedure are still under debate. Innovations in interventional therapy and better understanding of underlying diseases have improved therapy strategies. The aim of this study was the analysis of patient and disease characteristics, outcome, and specific complications. Between September 1988 and December 2006 we performed 42 orthotopic liver transplantations (OLTs) in 39 patients with BCS. A total of 29 (74%) women and 10 men (26%) had a median age of 35 years; the median follow-up period was 96 months. Etiologically, 27 patients had a preoperative diagnosis of hematologic disease, including myeloproliferative disorders (MPD), followed by factor V Leiden mutation and antiphospholipid syndrome. The actuarial 5-year and 10-year survival rates were 89.4% and 83.5%, respectively, compared to 80.7% and 71.4%, respectively, for other indications (n = 1742). Retransplantation was necessary in 3 patients (7.1%) with portal vein thrombosis or recurrent BCS. Although the number of bleeding events was similar, incidence of vascular complications was significantly higher in patients with BCS. Thrombosis of the portal vein was observed in 4.8% versus 0.8% of the patients, whereas liver veins were affected in 7.1% versus 0.2%. Our data shows that severe acute or chronic forms of BCS with liver failure can be successfully treated by OLT. Despite higher rates of vascular complications, patient and graft survival are similar or even better compared to other indication groups. In conclusion, patients with reversible hepatic damage should be treated by combined strategies, including medical therapy and surgical or interventional shunting.