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The co-reactivation of cytomegalovirus (CMV) and Epstein-Barr virus (EBV) in patients undergoing hematopoietic stem cell transplantation (HSCT) has been found. Research has shown that the reactivation of CMV or EBV is closely related to poor HSCT outcomes. In this study, we describe the clinical characteristics of HSCT patients with co-reactivation of CMV and EBV. We retrospectively reviewed the medical records of 327 patients who underwent HSCT at the Peking University People’s Hospital Institute of Hematology. Co-reactivation of CMV and EBV was observed in a total of 75 patients (22.9%) who also had a higher incidence of hemorrhagic cystitis (P=0.000). HSCT patients with CMV and co-reactivation of CMV and EBV had a significantly lower 1-year overall survival (OS; P=0.050). Further, COX regression analysis showed that viral infection was a risk factor for 1-year OS (HR, 12.625 for co-reactivation vs. no reactivation, p=0.021, and HR 13.580 for CMV reactivation vs. no reactivation, P=0.013). In conclusion, the patients with CMV reactivation had poorer outcome after HSCT regardless of EBV reactivation.