Antiphospholipid syndrome (APS) is an acquired thrombophilic disorder characterized by autoantibodies to cell membrane phospholipids. While altered coagulation can complicate end-stage liver disease, there are few reports describing the perioperative management for liver transplantation in recipients with a preexisting hypercoagulable disorder, such as APS. We present a patient with a history of APS, Budd-Chiari syndrome with cirrhosis, hepatopulmonary syndrome, and heparin-induced thrombocytopenia who underwent liver transplantation complicated by hepatic artery thrombosis. Management included postoperative anticoagulation with a factor Xa inhibitor and, after repeat transplantation, transition to long-term anticoagulation therapy with eventual recovery.