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Introduction: Elderly acute myeloid leukemia (AML) patients with poor‐risk cytogenetics have a poor outcome with intensive chemotherapy (IC). While Venetoclax (VEN) has changed the outcomes of elderly unfit patients treatment, it is unknown whether it could be effective in poor‐risk cytogenetics 60–75 years old patients. Materials and Methods: We included 60–75‐year‐old AML patients eligible to allogenic stem cell transplantation (allo‐SCT) treated with VEN (combined with azacitidine or with Cladribin and Aracytine) at Institut Paoli Calmettes, between 2020 and 2023 and compared this cohort with patients treated by IC between 2010 and 2019. Results: Twenty six patients were treated with VEN (17 in combination with azacitidine and 9 with Cladribin and Aracytine) and 90 were treated with IC. Thirteen patients (50%) had a TP53 mutation. The median time for leucocyte and platelet counts recovery was 26 days (range 0–103) and 26 days (range, 0–63). The median duration of the first hospitalization was 32 days (ranges, 7–79). The composite response rate was 69% (CR = 50%, CRi = 4%, MLFS = 15%). Allo‐SCT could be performed in 42% of cases. Median overall survival (OS) was 7.9 months (20.9 months in the group of patients who transitioned to allo‐SCT). We found no difference with the historical cohort of patients treated with IC except a trend toward less lower and upper tract gastro‐intestinal (GI) tract infections in the VEN group (respectively 8% vs 26%, p =.06; and 0% vs. 13% p =.06). Conclusion: VEN‐based treatment was found to be effective in high risk AML can be considered as an alternative to IC in patients aged 60–75 with adverse cytogenetics. [ABSTRACT FROM AUTHOR]