Standard-dose prednisone as first-line therapy for primary immune thrombocytopenia (ITP) can not obtain high long-term responses. Results from high-dose dexamethasone course administered in adult newly diagnosed ITP were promising. The role of standard-dose rituximab in first-line treatment of newly diagnosed ITP were also investigated. We retrospectively analyzed the efficacy and safety of high-dose dexamethasone plus low-dose (100 mg/w) rituximab for treatment of adults newly diagnosed ITP. A total of eighteen patients received dexamethasone 40 mg/day for 4 consecutive days (days + 1 to +  4), rituximab 100 mg once weekly for a total of 4 weeks (days + 7, + 14, + 21 and + 28). Non-responders accepted the repeated dexamethasone treatment every 2 weeks for a total of up to 3 treatment cycles. The overall response was 100% at 28th day. Median follow-up was 17 months (1-33 months). Six patients (33.3%) relapsed. Sustained complete response or response after 6 months and 12 months of follow-up were reached in 83.3% (15/18) and 61.5% (8/13) of patients respectively. The 12-month and 15-month cumulative relapse-free survival were 69.3% and 60.7%. Incidence of adverse effects was 11.1% (2/18). High-dose dexamethasone plus low-dose rituximab therapy had high efficacy and well tolerability as first-line treatment option in newly diagnosed ITP.