Severe veno-occlusive disease (VOD) of the liver is a frequent cause of morbidity and mortality in patients undergoing transplantation. While surgical portosystemic shunts have been reported to be useful in the treatment of severe hepatic VOD with intractable ascites, few of these patients are surgical candidates. We report a case of severe VOD after autologous peripheral blood progenitor cell transplantation treated with transjugular intrahepatic portosystemic shunting (TIPS). This procedure resulted in marked improvement in the patient's ascites, coagulation status and urinary output. The safety and efficacy of this non-surgical approach for the treatment of patients with severe VOD requires prospective studies.