BACKGROUND Patients are frequently exposed to heparin during hemodialysis (HD) to prevent thrombosis of the extracorporeal circuit. Other groups with frequent heparin exposures have a high rate of development of heparin-associated antiplatelet antibodies (HAAb). We sought to define the prevalence of HAAb in HD patients and evaluate their effects. METHODS A chart listing of all patients undergoing HD at our tertiary care institution during a six-year period was obtained. Charts of patients who tested positive for HAAb were reviewed. A cohort of randomly selected HD patients who tested negative for HAAb was analyzed as a control group. RESULTS In our sample, 3.7% of HD patients were positive for HAAb. Morbidity, as defined by thromboembolic (TEC) or hemorrhagic complications, was higher in the HAAb-positive group compared with the control patients (60% vs 8.7%, P < .05), and the mortality rate (mortality directly related to TECs) was also higher in the HAAb-positive patients (28.6% vs 4.35%, P < .05). CONCLUSIONS Contrary to reports of HAAb in patients undergoing HD without increased morbidity and mortality, we found significant increases in both morbidity and mortality. The elevated morbidity and mortality may represent ongoing endothelial and platelet activation from repeated heparin exposures. Reduced morbidity and mortality will likely require early recognition of HAAb and alteration of anticoagulation in HD patients.