Intensive chemotherapy (IC) is commonly used to achieve remission in patients with acute myeloid leukemia (AML). Venetoclax plus azacitidine (VEN-AZA) is FDA-approved to treat patients with AML aged ≥ 75 years or who are ineligible for IC. This retrospective analysis used de-identified electronic health records from the US-based Flatiron Health database from patients diagnosed 11/21/2018 to 10/31/2021 to compare treatment outcomes with VEN-AZA vs. IC. Patients were 1:1 propensity score-matched (\documentclass[12pt]{minimal}
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				\begin{document}$$N=276$$\end{document}N=276). Assessments included rates of complete remission (CR) and hematopoietic stem cell transplant (HSCT), overall survival (OS), and relapse-free survival (RFS). CR and HSCT rates were higher with IC than with VEN-AZA (60.9% vs. 44.2% [P= 0.006] and 18.1% vs. 8.0% [P= 0.012], respectively). Median OS was 17.7 months in patients treated with IC and 11.3 months with VEN-AZA without censoring (P= 0.278) and 13.7 vs. 10.6 months, respectively, with censoring at HSCT (P= 0.584). Median RFS was 12.0 months in patients treated with IC vs. 9.5 months with VEN-AZA without censoring (P= 0.431) and 6.4 vs. 7.4 months, respectively, with censoring at HSCT (P= 0.444). No OS or RFS differences observed between the two arms reached statistical significance. Randomized controlled trials comparing the two approaches are warranted, as are novel approaches to reduce relapse rates following CR.Supplementary InformationThe online version contains supplementary material available at 10.1007/s00277-023-05109-5.