Antiphospholipid syndrome (APS) is an autoimmune disease, and its most critical pathologic process is thrombosis, which may explain most of the clinical features. Acute management of thrombosis involves immediate anticoagulation. Acute proximal venous thrombosis can be managed with thrombolytic therapy to reduce the long-term complications of the postthrombotic syndrome (pain, swelling, skin discoloration, or ulceration) and perform recanalization of occluded vessels. However, thrombolytic therapies are associated with high risks of bleeding. To our knowledge, this is the first report of epidural hematoma mimicking transverse myelitis after catheter-directed thrombolysis in a patient with primary APS. A 42-year-old male was admitted with sudden onset pain and swelling on left lower extremity. Venography demonstrated multiple thrombi on superficial femoral vein, common femoral vein, common iliac vein, and external iliac vein. Laboratory tests indicated the presence of IgM anticardiolipin antibody. He was diagnosed with primary APS with multiple venous thrombi. He was treated with urokinase (200,000/h) as thrombolytic therapy. After 1 day, he complained both leg weakness and urinary dysfunction. T1- and T2-weighted magnetic resonance images of spine showed about 8 cm-sized mass, suggesting hematoma on the posterior epidural space at thoracolumbar area. Despite the successful evacuation of hematoma, neurologic symptoms persisted and he is now receiving aspirin, warfarin, and physical therapy.