Background Budd-Chiari syndrome (BCS) is a rare, potentially fatal disease characterized by hepatic venous outflow tract obstruction. Heparin-induced thrombocytopenia (HIT) is an immune-mediated complication of heparin therapy, with mortality approaching 10%. The reported prevalence of HIT in adults is 0.2-5.2%. Expert consensus through case reports is the only existing evidence of HIT in BCS. To our knowledge, this is the first study to formalize this anecdotal evidence. Methods A retrospective analysis was carried out of patients presenting at a tertiary liver centre with acute liver failure because of BCS or BCS as the primary indication for liver transplantation between 2000 and 2013. The prevalence of HIT in the study group was compared with the highest reported prevalence in adult medical patients receiving heparin (5.2%). Mortality, length of stay and liver transplantation rates were also studied. Results Of 32 BCS patients, 9 (28.1%) developed HIT, significantly higher than the previously reported prevalence of HIT in medical patients (5.2%) (P<0.0001). There was no difference in mortality (P=0.66), length of stay (P=0.58) and liver transplantation rate (P=0.39) between HIT-positive and HIT-negative patients. Conclusion The prevalence of HIT (28.1%) in our cohort of BCS patients is significantly higher than that in the general population (0.2-5.2%). Although this study was not powered to detect outcome differences, as heparin is the mainstay of acute BCS treatment, this represents a significant risk. We recommend a high index of suspicion for HIT in patients with BCS and thrombocytopenia, an appropriate HIT-testing strategy and consideration of direct thrombin inhibitors. Eur J Gastroenterol Hepatol 28:967-971 Copyright (C) 2016 Wolters Kluwer Health, Inc. All rights reserved.