Abstract: Objective To investigate the risk factors and prognosis of secondary thrombocytopenia after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Methods A total of 264 patients who received allo-HSCT in the Affiliated Hospital of Xuzhou Medical University from January 2013 to June 2020 were selected and their clinical data were retrospectively analyzed. According to the platelet count (PLT) of +60 days after transplantation, the patients were divided into two groups: a thrombocytopenia group (PLT<30×10⁹/L) and a control group (PLT≥30×10⁹/L). The risk factors and prognosis of thrombocytopenia were analyzed. Results The thrombocytopenia group showed a significantly higher infection rate of cytomegalovirus (CMV) than the control group (P=0.002). According to multivariate analysis, CMV infection was an independent risk factor for secondary thrombocytopenia. The 1-year and 3-year overall survival (OS) rate and disease-free survival (DFS) rate in the thrombocytopenia group were remarkably lower than those in the control group, while the 1-year and 3-year non-relapse mortality (NRM) in the thrombocytopenia group was higher than that in the control group (P<0.001). Multivariate analysis showed that +60 d PLT<30×10⁹/L was an independent risk factor affecting OS rate, DFS rate and NRM rate (P<0.001). Conclusions CMV infection is associated with secondary thrombocytopenia after allo-HSCT, and the prognosis of patients with secondary thrombocytopenia is poor.