Haemolytic uraemic syndrome (HUS) is characterized by nonimmune haemolytic anaemia, thrombocytopenia and renal impairment-most incidents in childhood are caused by shiga toxin-producing bacteria. Atypical HUS (aHUS) accounts for 10% of cases and has a poor prognosis. About 60% of patients with aHUS have dysregulation of the alternative complement pathway (complement-mediated aHUS). The kidney is the main target organ, but other organs might also be affected. Cardiac complications occur in 3-10% of patients with complement-mediated aHUS, as a consequence of microangiopathic injury in the coronary microvasculature, and can cause sudden death. Emerging evidence also suggests that either thrombosis or stenosis of the medium and large arteries might complicate disease course, and such disorders occur even after renal function is lost. In this Perspectives article we discuss the impact of cardiovascular involvement in complement-mediated aHUS, the role of acute and chronic complement hyperactivation in such events and the implications for treatment.