Objective:To evaluate the efficacy and safety of treating allogeneic hematopoietic stem cell transplantation (allo-HSCT) with azacitidine plus BUCY2 as a conditioning regimen for acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS).Method:From January 1, 2022 to July 15, 2023, a retrospective study was conducted for the relevant clinical data of 26 AML-MDS patients undergoing allo-HSCT with azacitidine plus BUCY2 as a conditioning regimen at Wuhan Union Hospital. There were 15 males and 11 females. For haploidentical transplantation, rabbit anti-human thymocyte immunoglobulin (ATG) was added. And tacrolimus + mycophenolale mofetil + recombinant humanized anti-CD25 monoclonal antibody injection (Xenopax) ± methotrexate were utilized for preventing GVHD. For human leukocyte antigen matched transplantation, cyclosporin A + methotrexate + Xenopax were employed for preventing GVHD. Incidence timing, severity, incidence rate of acute/chronic graft versus host disease (a/cGVHD), granulocyte/platelet engraftment time, infection type, overall survival and relapse date were recorded.Result:Granulocyte engraftment was attained with a median engraftment time of 12 (9~18) day and platelet engraftment with a median engraftment time of 16 (13~34) day. The incidence of acute graft-versus-host disease (aGVHD) was 63.14% (95% CI: 60.90%~65.37%), the incidence of grade Ⅲ aGVHD 6 (95% CI: 11.39%~13.23%) and the median onset time of aGVHD 49 (11~93) day post-transplantation. The incidence of chronic graft-versus-host disease (cGVHD) was 52.68% (95% CI: 49.23%~56.13%) and the incidence of moderate-severe cGVHD 11.43% (95% CI: 10.20%~12.66%). Infections were caused by cytomegalovirus (CMV) viremia (7 cases), bacteria (3 cases) and fungus (4 cases). Until the last follow-up, 23 recipients achieved relapse-free survival and continued MRD negativity. Death occurred due to recurrence (2 cases) and GVHD plus severe infection (1 case). Cumulative incidence of relapse (CIR) was 10.20% (95% CI: 9.21%~11.18%), 1-year overall survival (OS) 83.50% (95% CI: 67.90%~100%), GVHD/relapse-free survival (GRFS) 70.30% (95% CI: 52.30%~94.30%) and non-relapse mortality (NRM) 5.02% (95% CI: 4.53%-5.52%). Conclusion:Using azacitidine plus BUCY2 as a conditioning regimen, OS of allo-HSCT for AML-MDS is higher than that of traditional regimen. The risks of III-IV aGVHD, relapse and infection are safe and controllable.