Human immunodeficiency virus (HIV) infection is a risk factor for thrombotic microangiopathy (TMA). We sought whether a severe deficiency in ADAMTS13, the enzyme specifically involved in the cleavage of von Willebrand factor, was associated with specific presenting features and outcome in HIV‐associated TMA. In this prospective, multicentre, case–control study, 29 patients of 236 in the French Network on TMA had an HIV‐associated TMA. Seventeen patients with severe ADAMTS13 deficiency (ADAMTS13 <5% HIV+ group) were compared to 12 patients with a detectable ADAMTS13 activity (ADAMTS13 ≥5% HIV+ group). HIV+ patients were also compared to 62 patients with idiopathic TMA, either with (45 patients, ADAMTS13 <5% idiopathic group) or without (17 patients, ADAMTS13 ≥5% idiopathic group) severe ADAMTS13 deficiency. ADAMTS13 <5% HIV+ patients had less AIDS‐related complications than ADAMTS13 ≥5% HIV+ patients (23.5% versus 91.6%, respectively, P = 0.0005) and their median CD4+ T cell count was higher (P = 0.05). TMA‐associated death rate was higher in ADAMTS13 ≥5% HIV+ patients than in ADAMTS13 <5% HIV+ patients (50% versus 11.7%, respectively, P = 0.04). In ADAMTS13 <5% patients, TMA‐associated death rate was comparable between HIV+ and idiopathic patients (15.5% in idiopathic patients, P‐value was non‐significant). By contrast, TMA‐associated death rate in ADAMTS13 ≥5% HIV+ patients was higher than in idiopathic patients (11.7% in idiopathic patients, P = 0.04). In conclusion, HIV‐associated TMA with severe ADAMTS13 deficiency have less AIDS‐related complications and a higher CD4+ T cell count. TMA prognosis is better and comparable to this of idiopathic forms.