The combination of venetoclax (VEN) with hypomethylating agents (HMAs) improves survival in patients with acute myeloid leukemia (AML) and may cause neutropenia requiring combined antifungal therapy or prophylaxis. The inhibition of cytochrome P450 activity by azole antifungal agents leads to elevated blood concentrations of VEN. This study aimed to evaluate the efficacy and safety of venetoclax plus azacitidine (AZA) with azoles in newly diagnosed AML patients. The primary endpoints included complete remission (CR), complete remission with incomplete blood cell recovery (CRi), composite CR (CRc, CR + CRi), blood cell recovery time and incidence of infections. The CRc was 50.0% in the azole group and 56% in the nonazole group ( > 0.05). In the azole group, the median recovery times for patients with ANC >500 cells/mm and ANC >1,000 cells/mm were 19 and 25 days, respectively. For the nonazole group, the corresponding times were 16 and 19 days ( < 0.05). In the azole group, the median durations for patients with a PLT >50,000/mm and >100,000/mm were 18 and 20 days, respectively. For the nonazole group, the corresponding times were 16 and 19 days ( > 0.05). The incidences of fungal and bacterial infections were not significantly different (30.8% vs 26.1% and 50.0% vs 56.0%) ( > 0.05). The cost-effectiveness ratio of the azole group is lower. There was no significant difference between VEN + AZA with or without azole in terms of efficacy, infection, or partial hematological toxicity. However, the combination of azoles may prolong the neutrophil recovery time. Azole combination could reduce the amount of venetoclax and improve health economics.