Plasma exchange (PE) is considered first-line treatment for thrombotic thrombocytopenic purpura (TTP) to the point that many clinicians regard it as definitive therapy. Studies have reported response rates to PE ranging from 39% to 78%. In our experience, a minority of patients have been cured solely by PE. While adjuvant therapies (e.g., vincristine, splenectomy) have proved effective in anecdotal reports, protocols using these therapies in the treatment of TTP have not been established. Management of TTP over a 15-year period was reviewed to evaluate (1) the rate of cure accomplished by PE alone, and (2) the potential benefit of additional therapies. The records of 29 consecutive patients with TTP treated by PE were reviewed and classified according to response to PE alone and the need for adjuvant therapy. Eight patients (28%) achieved remission and long-term survival with PE alone. With the addition of adjuvant therapy another 13 patients survived, bringing the total survival to 72%. Fifteen patients were treated with vincristine in addition to PE. Only three of seven patients receiving vincristine after failing to respond completely to PE survived, but survival increased to 88% (7 of 8) when vincristine was administered within 3 days of beginning PE. These data suggest that PE alone may not be sufficient therapy for most patients with TTP. Additional therapy is often needed to achieve long-term survival. While controlled trials will be necessary to prove the efficacy of vincristine, we believe that, given the minimal risk of vincristine toxicity and the grave consequences of ineffective therapy, routine administration of vincristine early in the course of PE should be considered.