Objective To investigate the efficacy and safety of the optimal alkalized hydration solution for hemorrhagic cystitis (HC) following unrelated donor allogeneic hematopoietic stem cell transplantation (URD-HSCT), and the risk factors and prophylaxis measures about HC.Methods The clinical data of 151 HC patients who underwent URD-HSCT were retrospectively analyzed. All patients were given busulfan/cyclophosphamide (BuCy)-based conditioning regimen.During Cy therapy, all patients were given the optimal alkalized hydration solution to prevent HC.MESNA was given intravenously after administration of Cy at 0, 3, 6, 9, 12 h, and its total dose was administration of Cy to 24 h under the ECG monitoring. Each 500 ml liquid contained 50 g/L sodium bicarbonate 20 ml. Urinary pH value was monitored every one hour (keeping urine pH＞7. 5). Results None of early onset HC occurred. Twenty-six of 151 (17. 2 %) patients developed late onset HC, and the median onset time was 40 (8～89) days after transplantation. During the therapy, no symptoms of the circulatory system, no congestive heart failure and no acid-base electrolyte imbalance occurred. All HC patients after re-hydration, diuretic, and (or) continuous bladder irrigation and other indwelling catheter after treatment, were cured. The statistical analysis showed that the following factors were significantly associated with HC: male (OR = 3. 093, 95 % CI, 1. 145～8.353, P＜0. 05), acute graft versus host disease (aGVHD) (OR= 18. 044, 95 % CI, 3. 952～～82. 392, P＜0. 01), and ≥30-yearold (OR = 6. 077, 95 0% CI, 1. 585～23. 299, P＜0. 01). Conclusion The optimal alkalized hydration solution is safe and effective to prevent early onset HC following URD-HSCT in combination with BuCy regimen. Male, aGVHD and ≥30-year-old were the risk factors for HC.