Background: Initial induction chemotherapy is critical for patients with newly diagnosed de novo acute myeloid leukemia (AML). The aim of the present study was to analyze the factors affecting the outcome of patients with AML who failed to initial chemotherapy. Materials and Methods: We retrospectively analyzed clinical data of 311 adults with de novo AML. Results: Compared with 179 patients showing complete remission (CR), 132 patients who failed to achieve CR were older with poorer prognostic stratification, higher proportion of FLT3-ITD mutations, higher expression rates of CD9, lower expression rates of cMPO and CD64 and poorer overall survival (OS). The 2-year OS rate of the non-CR groups was inferior to that of the CR groups (28.3% versus 53.3%, P < 0.001). However, there was no dramatic difference in 2-year OS rate between initial and reinduction chemotherapy if patients achieved a same remission status. The 2-year OS rate significantly improved following allogeneic hematopoietic cell transplant in patients who failed to initial treatment. The survival of patients with similar remission status was affected by FLT3-ITD mutation instead of CD9(+) expression. Conclusions: Initial induction failure or poorer prognostic stratification seriously affected the survival of patients with de novo AML. The allogeneic hematopoietic cell transplant is an alternative strategy to improve the survival of patients resistant to initial treatment.