The purpose of this study is to assess the incidence and describe the clinical and pathological features of macrovascular thrombosis during the course of thrombotic micro-angiopathy (TMA) in a 6 year retrospective study of all adults with TMA, admitted to a teaching-hospital ICU. Of the 55 patients identified, all had anaemia and thrombocytopenia and 45 (82 %) had renal or neurological impairment. All patients received plasmapheresis, steroids, and strict blood pressure control. Macrovascular venous or arterial thromboses were diagnosed in 28 (51 %) patients; among them, 7 had cerebral artery thrombosis and 21 (including 13 with central venous catheters) had deep vein thrombosis. Median time from plasmapheresis initiation to thrombosis was 7 (4-10) days. Clinical findings were suggestive of deep venous thrombosis in 7 of the 21 patients (33 %) and only one of the 7 patients with stroke had corresponding clinical signs. By multivariate analysis, factors independently associated with macrovascular thrombosis were undetectable ADAMTS13 activity (odds ratio 7.33, 95 % confidence interval 1.3-41.3), cardiac involvement with TMA (odds ratio, 3.46; 95 % confidence interval, 1.1-13.9) and TMA flare (odds ratio 9.03; 95 % confidence interval 1.03-79.4). In conclusion, half of the patients with TMA experience macrovascular thrombosis. Patients with TTP-related ADAMTS13 deficiency and those with cardiac manifestations of TMA are at higher risk for arterial or deep venous thrombosis.