Antiphospholipid syndrome (APS) is a disorder characterized by recurrent venous or arterial thrombosis and/or fetal loss; involvement of cardiac valves is also seen. A seronegative variant has been described previously. We report a case of a woman with recurrent pregnancy loss, prior strokes, and a negative workup for known antiphospholipid antibodies. During her current pregnancy, she presented with acute stroke and mitral valve vegetation. Her workup for antiphospholipid syndrome and other thrombophilias remained negative even after the stroke. Her mitral valve vegetation resolved completely with aspirin, heparin, and warfarin. We believe this to be the first report of complete resolution of valvular vegetation with antiplatelet and anticoagulant therapy alone in a patient with seronegative antiphospholipid syndrome. Moreover, this appears to be the first report of stroke associated with this condition.