Background: Multiple therapeutic interventions are available for treatment of thrombotic thrombocytopenic purpura. Resolution of thrombotic thrombocytopenic purpura may require use of several of these interventions. Case Report: A patient presenting with classic (non-cancer chemotherapy-associated) thrombotic thrombocytopenic purpura had an initial response to intensive, daily plasma exchange with fresh-frozen plasma and cryosupernatant. Multiple attempts over a period of 2 months to;decrease the frequency of plasma exchange resulted in exacerbations of disease activity, indicated by increased schistocytosis, decreased hematocrit, increased serum lactate dehydrogenase, and decreased platelet counts. After a total of 39 plasma exchanges, the patient was begun on immunoadsorption therapy utilizing a staphylococcal protein A immunoadsorption treatment column. After six 2000-mL protein A immunoadsorption treatments, the patient's platelet count, lactate dehydrogenase, and peripheral smear normalized, and they have remained normal over nearly 4 months of follow-up. Conclusion: Treatment by protein A immunoadsorption may be of benefit in patients with classic thrombotic thrombocytopenic purpura who are not achieving a sustained remission with conventional plasma exchange therapy.