Post-hematopoietic stem cell transplantation (HSCT) relapse is one of the main complications of HSCT in patients with higher-risk myelodysplastic syndromes (MDS). Combined use of donor lymphocyte infusion (DLI), hypomethylating agent (HMA), and cytokines, as well as risk-directed stratification management measures may improve the outcomes of higher-risk MDS after HSCT. The risk-directed stratification management measures include pre-emptive interventions for MRD positive (MRD+) higher-risk MDS patients, prophylaxis and maintenance therapy for very high risk patients, and salvage therapy for hematological relapsed patients. This article focuses on the treatment measures of high-risk MDS patients who relapse after HSCT, intervention strategies of stratification of relapse risk based on MRD detection , as well as maintenance treatment of high-risk MDS patients after HSCT and the prevention strategies for relapse.