Therapeutic plasma exchange (PE) is the accepted therapy for thrombotic thrombocytopenic purpura (TTP). Because not all patients achieve remission, other treatment modalities have been used in addition to PE, but no randomized clinical trial evaluated their efficacy. The aim of this multicentric study was to compare the effectiveness of standard- versus high-dose methylprednisolone as an adjunctive treatment to PE in the acute phase of TTP. Sixty patients with idiopathic TTP were randomized to receive methylprednisolone 1 mg/kg/die intravenous or 10 mg/kg/die for 3 days, thereafter, 2.5 mg/kg/die in addition to PE. Both dosages of steroids were well tolerated. At the end of induction therapy (day 23), the percentage of patients failing to achieve complete remission was significantly higher in the standard dose (16 of 30) than in the high-dose group (seven of 30). Also, the number of cases without a good response at day 9 and the number of deaths were higher in the standard-dose arm, but the differences did not reach the statistical significance. Results of present study indicate that the association of PE with high-dose instead of standard-dose steroids reduces the percentage of TTP patients that fail to achieve complete remission.