Background and Objectives ABO blood group accounts for up to 40% of the variability in plasma von Willebrand factor (VWF) levels, which vary in the rank order AB > B > A > O > Bombay. This may be due in part to the influence of ABO-associated oligosaccharides on the proteolysis of VWF by the metalloprotease ADAMTS13, which is markedly deficient in thrombotic thrombocytopenic purpura (TTP). Using ABO blood group as a surrogate for baseline VWF levels as well as susceptibility to proteolysis by ADAMST13, we set out to determine whether ABO blood group influences the clinical course of TTP. Methods We conducted a retrospective analysis of the clinical course of 76 patients with primary, sporadic TTP treated at two institutions over the past 10 years. Results We found no significant differences between group O and non-O patients with respect to presenting platelet count and lactate dehydrogenase concentration, maximum serum creatinine concentration, and total number of therapeutic plasma exchanges per episode. Conclusions Substrate-related contributors to the highly variable phenotype and clinical course of TTP warrant further investigation. © 2009 International Society of Blood Transfusion.