BACKGROUND/PURPOSE: Extrahepatic portal vein obstruction (EHPVO) is an important cause of chronic portal hypertension in children. Although usually idiopathic in etiology, genetic and acquired thrombophilia have been implicated in EHPVO. Meso-Rex bypass is increasingly used to treat EHPVO in children. OBJECTIVE: The objective of this study is to assess the relationship of postoperative anticoagulation strategies and thrombophilic risk factors to the development of bypass thrombosis following the meso-Rex bypass. METHODS: Records of children who underwent meso-Rex bypass for EHPVO at a single institution from 1999 to 2009 were reviewed, and preoperative thrombophilia testing, perioperative anticoagulation strategies, and postoperative bypass patency based on imaging at last follow-up were examined. RESULTS: Sixty-five children with EHPVO underwent a first time meso-Rex bypass during the study period, and 9 of 65 (14 %) developed bypass thrombosis. The use of warfarin in the postoperative period was more common among children with thrombosed shunts than among those with open shunts [63 % vs. 20 %; OR, 6.5 (95 % CI, 1.3-31.5), p = 0.022]. The contribution of genetic or acquired thrombophilia to shunt thrombosis was inconclusive given variability in testing. CONCLUSIONS: Choice of anticoagulation following meso-Rex bypass may affect postoperative incidence of bypass thrombosis. Role of thrombophilic risk factors in the development of shunt thrombosis remains unclear.