Vascular damage in systemic lupus erythematosus (SLE) occurs through vasculitis, premature atherosclerosis, and hypercoagulability (predominantly due to the antiphospholipid antibody syndrome). In the Hopkins Lupus Cohort, a prospective cohort study, the incidence of thrombosis is 2 per 100 person-years of follow-up. Markers of immune-complex mediated injury (high anti-dsDNA and low C3), atherosclerosis (hypertension, hyperlipidemia, homocysteine) and antiphospholipid antibodies (lupus anticoagulant or anticardiolipin) are independent predictors of thrombosis. Hydroxychloroquine use is protective against future thrombosis.