Objective To study and summarize the clinical characteristics of the patients with acute myeloid leukemia (AML) who were intolerant to intensive chemotherapy screened by comprehensive geriatric assessment, and evaluate the efficacy and safety of different chemotherapy regimens for these patients. Methods From June 2018 to May 2021, in a total of 120 patients with newly diagnosed AML in our center, 52 cases screened as intolerance of intensive chemotherapy were selected and their clinical characteristics, induction safety and remission rate were analyzed retrospectively. Results The median age of the selected patients was 67.5 years old, and 9 cases were ≥75 years old. Thirty-eight patients (73%) had previous medical history or at least one comorbidity. Forty-seven cases were de novo AML and 5 cases were secondary AML. 54% cases had bone marrow blasts at the time of diagnose. A total of 50 patients completed cytogenetic and molecular assessment, in which, 4 patients had low-risk karyotypes, 25 patients had intermediate-risk and 21 patients had high-risk karyotypes. Among the high-risk karyotypes, there were 12 cases with complex karyotypes and monosomal karyotypes. The most common gene mutations were nucleophosmin 1(NPM1) (19 cases), DNA methyltransferase 3A (DNMT3A) (14 cases), Fms-related tyrosine kinase 3-internal tandem duplication (FLT3-ITD) (11 cases), ten-eleven translocation 2(TET2) (10 cases) and Runt-related transcription factor 1 (RUNX1) (9 cases). The cytogenetic/molecular risk stratification showed that 43 cases had intermediate (14 cases) or high risk (29 cases), which accounted for 86%. Eleven patients received only supportive treatment. Of 41 patients got chemotherapy, 25 cases received a combination treatment of hypomethylation reagent and venetoclax (HMA+VEN). Other traditional induction included decitabine combined with priming chemotherapy (6 cases), demethylation drug (4 cases), and reduced-dose idarubicin combined with cytarabine, priming chemotherapy and low-dose cytarabine (2 cases). The complete remission rate of HMA+VEN regimen reached 64%, which was better than that (31%) in the patients receiving traditional induction chemotherapy (P=0.004). In addition, the long-term survival of the HMA+VEN treatment group was also significantly better than that of traditional chemotherapy and untreated groups(P=0.001). Conclusions The elderly AML patients with intolerance of intensive induction have the characteristics of advanced age, complicated comorbidities, and adverse prognostic factors in cytogenetics and molecular. The new induction treatment of demethylation drugs and venetoclax has a good effect and will become one of the important regimens for elderly AML patients.