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Nowadays, the regular recommended dose of decitabine for the treatment of myelodysplastic syndrome (MDS) is 20 mg/m2/day for 5 consecutive days with a relatively high incidence of treatment-related morbidities and costs. In this study, a retrospective and multicenter analysis was performed to explore the very-low-dose decitabine schedule for the treatment of patients with IPSS intermediate- or high-risk MDS. A total of 31 newly diagnosed MDS cases from 14 hospitals in Beijing received decitabine monotherapy (decitabine 6 mg/m2/day intravenously for 7 consecutive days, repeated every 4 weeks). With a medium follow-up of 4 months, 10 patients achieved complete remission (32.3%), 8 (25.8%) partial remission, and 3 (9.7%) hematological improvement. The overall response rate (ORR) was 67.7%. Rates of 21.7% for severe infections and 11.6% for severe bleedings were observed among all courses. The median cost of each course was USD 5,300, 3,000, 2,900, and 2,000, respectively. Multivariate analysis identified bone marrow blast cells ≥10% and a Charlson comorbidity index ≥1 as 2 independent factors for efficacy. In conclusion, very-low-dose decitabine showed relatively good efficacy, good tolerance, and low medical cost in the treatment of intermediate- or high-risk MDS. Elderly patients with more than 1 complication or patients with a higher proportion of blast cells may be the most suitable candidates for this regimen.