The incidence of thrombotic microangiopathy (TMA) was retrospectively evaluated in a cohort of 1223 patients with acquired immunodeficiency syndrome (AIDS) who were observed from January 1985 through December 1996 (before the era of highly active antiretroviral therapy [HAART]), and the incidence was prospectively assessed for 347 patients with AIDS during the period of January 1997 through December 2000 (during the HAART era). Seventeen cases were reported in the former cohort (1.4%). The increased risk of developing TMA was statistically significant in patients with cryptosporidiosis or AIDS-related cancer but not in those with other diseases. In the 1997-2000 cohort, no cases were observed during follow-up. TMA is associated with conditions observed in the advanced phases of human immunodeficiency virus infection. The disappearance of TMA during the HAART era may be explained by the lower percentage of patients with long-lasting CD4+ T cell depletion, advanced AIDS, or cryptosporidiosis or who have undergone multiple courses of chemotherapy for treatment of cancer.