Objective To investigate the efficacy and safety of a schedule of 2 cycles' high-dose dexamethasone (HD-DXM) as an initial therapy in adults immune thrombocytopenia (ITP), and compare with conventional dose prednisone therapy. Method A total of 59 newly diagnosed ITP patients were divided into 2 groups randomly. In 30 patients ( Dexamethasone group), oral HD-DXM was administered at 40 mg/d for 4 consecutive days, repeated one week later, and then failed to maintain. In the remaining 29and then gradually tapered. Results For short-term efficacy, after 1 and 2 weeks of treatment, the response rate in Dexamethasone group was significantly higher than that in Prednisone group (50. 0% vs 24. 1%, P ＜0. 01; 73.3% vs 55.2%, P ＜0. 05 ), while 3 weeks later, there was no remarkable difference between the two groups(83.3% vs 68.9%, P ＞ 0. 05 ), though the response rate in Dexamethasone group remained higher. For long-term effect, at the end of the 2nd and 3rd months of follow-up, the relapse rate in Dexamethasone group was significantly lower than that in Prednisone group(24. 0% vs 40. 0%, P ＜ 0. 05;32.0% vs 65. 0%, P ＜ 0. 01 ), while at the end of the 1st month of follow-up, there was no significant difference( 16. 0% vs 20. 0%, P ＞0.05 ). In addition, it's well tolerated and no complications such as severe infection or Cushing syndrome were complained in Dexamethasone group. Conclusion HD-DXM possesses an advantage over conventional dose prednisone therapy in efficacy and safety.