An association between HIV infection and Thrombotic Thrombocytopenic Purpura (TTP) remains controversial. We conducted a cross-sectional analysis of 39 consecutive, non-referral cases of TTP encountered over 9 years at a single institution. Thirteen cases had HIV infection. The patients were treated with daily plasma exchange until remission. The mean (standard deviation) duration of follow-up was 48 (37) months. Seven patients died. TTP caused 3 of the 4 deaths in the HIV-group but none of the 3 deaths in the HIV+ groups. The age and sex adjusted incidence rate of TTP was 14.5 cases per 10 6 person-years. The relative risk of TTP was 38.5 (95% confidence interval, 19.7-75.0) for HIV infection, 2.7 (1.3-5.7) for female gender and was not increased for the black race. Neither HIV infection nor gender affect the overall and relapse free survivals. While relapse continued to occur throughout the follow-up period in the HIV-group, it did not occur in the HIV+ group after the first year. We conclude that HIV infection is a major risk factor of TTP. The risk of late TTP relapse is low in HIV infected patients treated with anti-retroviral therapies.