Antiphospholipid syndrome (APS) is an autoimmune disease characterized by venous thromboembolism, arterial thrombosis, and obstetric morbidities in the setting of persistently positive levels of antiphospholipid antibodies measured on 2 different occasions 12 weeks apart. Patients with APS are at increased risk for accelerated atherosclerosis, myocardial infarction, stroke, and valvular heart disease. Vascular endothelial cell dysfunction mediated by antiphospholipid antibodies and subsequent complement system activation play a cardinal role in APS pathogenesis. Improved understanding of their pathogenic function could help in the risk stratification of patients with APS and provide new molecular therapeutic targets. (C) 2017 by the American College of Cardiology Foundation.