Abstract: Objective  To investigate the expression of CD38 in non-M3 acute myeloid leukemia and its prognostic significance．Methods One hundred and twenty-three patients with non-M3 subtype of primary acute myeloid leukemia were enrolled in Chinese PLA General Hospital from January 2011 to December 2015． The expression level of CD38 on leukemic cells was detected by flow cytometry, and the patients were then divided into CD38⁺ group and CD38^- group． There were 52 males and 43 females with a median age of 42 years in CD38⁺ group, and 21 males and 7 females with a median age of 47．5 years in CD38^- group． The clinical characteristics and the survival status were analyzed between these two cohorts retrospectively．   Results  Patients in CD38^-group were associated with poorer risk stratification status (35．7% vs 21．1%, P= 0．02), lower complete remission rate (60．7% vs 84．2%, P=0．01), lower 3-year EFS (24．9% vs 36．8%, P=0．05) and 5-year OS (27．2% vs 36．2%, P=0．01) when compared with CD38⁺ group．Multivariate analysis also demonstrated that CD38^-could be an independent poor prognostic predicting factor (HR=1．7, P=0．048)．The 5-year OS rates of patients receiving allogeneic stem cell transplantation were superior to those in the patients not receiving transplantation in both CD38⁺and CD38^-cohorts (48．8% vs 26．0%, P=0．006; 53．3% vs 7．9%, P=0．02)． During the follow-up, the transformation of CD38⁺to CD38^-on the myeloid leukemia cells suggested disease progression．   Conclusion  The decreased expression of CD38 can be served as a predictor suggesting disease progression and poor prognosis in non-M3 acute myeloid leukemia． Allogeneic stem cell transplantation may improve the poor outcome of CD38^-patients．