Objective:To investigate the efficacy of azacitidine combined with CAG regimen in the treatment of acute myeloid leukemia (AML) patients who are not suitable for intensive chemotherapy.Methods:A retrospective case-series study was conducted. A total of 67 AML patients with newly diagnosed elderly, treatment-related secondary and myelodysplastic syndromes or myeloproliterative neoplasms primary transformation who were not suitable for intensive chemotherapy were selected from Heze Municipal Hospital from January 2020 to December 2023. Azacitidine combined with CAG regimen was given for treatment, and the efficacy and adverse reactions of the patients were observed.Results:Among the 67 patients, there were 32 females and 35 males with the median age [ M ( Q1, Q3)] of 68 (65, 72) years old. There were 40 cases in the high-risk group, 13 cases in the medium-risk group, and 14 cases in the low-risk group. After 1 course of treatment with azacitidine combined with CAG regimen, the overall response rate (ORR) was 38.8% (26/67), with a complete remission (CR) rate of 20.9% (14/67), a complete remission rate with incomplete recovery of blood cell count (CRi) of 11.9% (8/67), and a partial remission (PR) rate of 6.0% (4/67). After 4 courses of treatment, the ORR was 59.7% (40/67), with a CR rate of 56.7% (38/67) and a CRi rate of 3.0% (2/67). There were no PR patients. All patients in the low-risk and medium risk groups achieved at least CRi, while the ORR in the high-risk group was 40.0% (16/40). There was a statistically significant difference in efficacy between different risk groups ( P < 0.001). The patient had mild adverse reactions, mainly pain and grade 1-2 hematological adverse reactions. Conclusions:AML patients who are intolerant to intensive chometherapy are effectively treated with azacitidine combined with CAG regimen, and the adverse reactions are mild.