Abstract: OBJECTIVE To explore the risk factors for fungal infection in the patients with myelodysplastic syndrome（MDS） patients during chemotherapy and observe the effect of prophylactic antifungal treatment. METHODS The clinical data of 2 974 MDS patients who underwent chemotherapy in the First Affiliated Hospital of Soochow University from Jan 2018 to Jan 2020 were retrospectively analyzed, all of the patients received the prophylactic antifungal therapy and were divided into the posaconazole group with 927 cases, the voriconazole group with 1 263 cases, and the itraconazole group with 784 cases. The effects of antifungal agents and adverse reactions were compared. Totally 106 patients had fungal infection（ the infection group）, 120 patients were randomly chosen from the patients without fungal infection and set as the control group, the clinical data were compared between the two groups, and the risk factors for the fungal infection were analyzed. RESULTS Diabetes mellitus, agranulocytosis time and use of glucocorticoids were independent risk factors for the fungal infection in the MDS patients during chemotherapy（P＜0.05）, white blood cell（WBC） counts and prophylactic use of posaconazole were the protective factors（P＜0.05）. The number of cases of fungal infection was less in the posaconazole group than in the voriconazole group and the itraconazole group（P＜0.05）. There were no significant differences in the length of hospital stay and number of cases of death due to fungal infection among the three prophylactic regimens. The incidence rates of liver function damage and visual abnormalities of the posaconazole group were significantly lower than those of the voriconazole group and the itraconazole group（P＜0.05）. There were no significant differences in the incidence rates of rash, diarrhea, liver function damage and dizziness among the three prophylactic regimens. CONCLUSION The MDS patients are prone to have fungal infection during chemotherapy. It is necessary to actively identify the related risk factors and take interventions to the high risk patients by using antifungal agents so as to reduce the risk of infection, and posaconazole had certain advantages in the preventive effect and safety.