Background: Autoimmune idiopathic thrombocytopenic purpura (ITP) is a common hemolytic disease in which platelets are destroyed in the reticuloendothelial system by the opsonization of antiplatelet antibodies, leading to thrombocytopenia and spontaneous skin and mucosal hemorrhage (epistaxis, gingival hemorrhage, GI hemorrhage). Glucocorticoids especially prednisolone are generally used in the treatment of ITP, which causes several mental and physical adverse effects, particularly if used in long terms.Methods: This randomized clinical trial study was conducted in 80 ITP patients from 5 hospitals. Subjects were divided to two groups by random allocation, 40 patients received oral prednisolone with conventional dose of 1mg/kg/day and 40 patients received 0.5mg/kg/day oral prednisolone (low dose group). The two groups were matched with respect to age and sex. Patients were studied for 14 months and platelet count (the main indicator for treatment response) was checked before treatment and at the end of 3rd and 24th months. Findings: 90% of patients (n=72) showed complete or relative response to oral prednisolone therapy. There was not any significant difference between groups regarding response to treatment (p>0.05). Splenectomy were performed in 8 patients due to failure of medical therapy, and showed no significant difference between the groups (p>0.05).Conclusion: Comparing normal and low dose steroid therapy, the latter carries similar response rate, lower adverse effects and better patient's compliance. Thus, we recommend low dose therapy for the initial treatment of ITP.