Antiphospholipid antibody syndrome (APS) is a coagulation disorder associated with antiphospholipid antibodies. Headache is common in APS patients and often unresponsive to analgesics. We report a case of refractory headache in a patient with APS, who was improved by high-intensity warfarin treatment. The mechanisms of the headache in patients with APS were presumed to be hypercoagulability of microcirculation and thrombotic occlusion of the capillaries, which were associated with antiphospholipid antibodies. Therefore, high-intensity warfarin could be considered as one of the treatments for refractory headache in patients with APS.