Thrombotic thrombocytopenic purpura (TTP) and hemolytic-uremic syndrome (HUS) represent multiple disorders with diverse etiologies. We compared the gender and race of 335 patients enrolled in the Oklahoma TTP-HUS Registry across 21 years for their first episode of TTP or HUS to appropriate control groups. The relative frequency of women and white race among patients with TTP-HUS associated with a bloody diarrhea prodrome and the relative frequency of women with quinine-associated TTP-HUS were significantly greater than their control populations. The relative frequency of women and black race among patients with idiopathic TTP and TTP associated with severe ADAMTS13 deficiency was significantly greater than their control populations. The relative frequency of black race among patients who had systemic lupus erythematosus (SLE) preceding TTP was significantly greater than among a population of patients with SLE, and the relative frequency of black race among patients with other autoimmune disorders preceding TTP was significantly greater than their control population. No significant gender or race disparities were present among patients with hematopoietic stem cell transplantation-associated thrombotic microangiopathy, TTP associated with pregnancy, or TTP associated with drugs other than quinine. The validity of these observations is supported by the enrollment of all consecutive patients across 21 years from a defined geographic region, without selection or referral bias. These observations of different gender and race disparities among the TTP-HUS syndromes suggest the presence of different risk factors and may serve as starting points for novel investigations of pathogenesis.