Background: Venetoclax-based (ven) combinations have become a standard of care for acute myeloid leukemia (AML) patients ineligible for intensive chemotherapy. However, the associated risk of infectious adverse events (IAEs) remains a significant clinical concern. Aims: This study aimed to evaluate the incidence, characteristics, and risk factors for IAEs in newly diagnosed AML patients treated with venetoclax combinations in a real-world setting. Methods and Results: We conducted a retrospective cohort study of AML patients treated with ven in combination with hypomethylating agents or low-dose cytarabine (LDAC), with analyses performed on a treatment cycle basis. Clinical and laboratory data, including IAE characteristics, duration of neutropenia, and concomitant medications, were collected, and grade ≥2 IAEs were included according to CTCAE v5.0 criteria. The cohort included 143 treatment cycles of 43 patients, with a median neutropenia duration of 13 days (5–35). A total of 34 (23.8%) grade ≥2 IAEs occurred, with an incidence of 1 per 121 patient-days. Multivariate analysis identified prolonged neutropenia (days, OR=1.037, p=0.005) and interacting concomitant medications (OR=9.99, p<0.001) as independent risk factors for IAEs. The rate of invasive fungal infections was as low as 3.5%, and the use of antifungal or antibacterial prophylaxis was not associated with a reduction in the rate of IAEs. Conclusion: IAEs remain a substantial risk in venetoclax-treated AML patients, particularly during prolonged neutropenia and with concomitant drug interactions. Optimizing venetoclax regimens and careful management of interacting medications may mitigate these risks.