The prognosis and optimal management of patients with thrombotic thrombocytopenic purpura (TTP) who fail initial therapy with plasmapheresis or splenectomy are unclear. We report our experience with eight patients with TTP who did not respond to initial therapy. Seven patients achieved complete remission when alternate therapy was started soon after the recognition of initial treatment failure. One patient who received no alternative therapy died of progressive TTP. Our cases combined with those in the literature indicate a 74% salvage rate for patients who fail initial treatment for TTP. The combination of splenectomy, dextran, and steroids appears to be an effective treatment for patients with TTP who fail to respond adequately to plasmapheresis.