High-dose dexamethasone (HDD) has been shown to be an effective initial treatment for immune thrombocytopenia (ITP), but it is not clear whether HDD offers any advantages over conventional-dose prednisone (PSL). We retrospectively compared the efficacy and toxicity of HDD and PSL for newly diagnosed ITP. The response was evaluated according to the International Working Group (IWG) criteria. We analyzed data from 31 and 69 patients in the HDD and PSL groups, respectively. There were no significant differences in patient characteristics between the two groups except for the incidence of the eradication of Helicobacter pylori. The response rate was better in the HDD group (42.7 vs. 28.4 %), and this difference was statistically significant when adjusted for other factors including the eradication of H. pylori. In the HDD group, a response was achieved earlier (28 vs. 152 days in median) and steroids were more frequently discontinued at 6 months (64.5 vs. 37.7 %). Among patients who achieved a response, there was no significant difference in the incidence of loss of response. There were no significant differences in the rate of adverse events, transition to chronic ITP, and splenectomy. In conclusion, HDD might enable the early cessation of steroids without a loss of response.