While thrombotic thrombocytopenic purpura (TTP) has a mortality rate of approximately 10% even when treated, predictors of mortality are unknown. In a prospective cohort registry of 292 TTP patients with 312 episodes of TTP in the United Kingdom, factors associated with mortality were evaluated. TTP patients with high amounts (top quartile) of a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 (ADAMTS13) antibody had significantly higher mortality than those in the lowest quartile (16.9% vs. 5.0%, P=0.004). In addition, those patients with ADAMTS13 antigen level in the lowest quartile (<1.5%) had significantly higher mortality than those in the highest quartile (>11%) (18.0% vs. 3.8%, P=0.005). Furthermore, patients in the lowest quartile for ADAMTS13 antigen and the highest quartile for ADAMTS13 antibody had an increased mortality rate of 27.3%. Individuals who presented with elevated troponin levels on hospital admission also had increased mortality. Careful screening, monitoring and aggressive treatment are needed for those individuals at highest risk of mortality.