Background: Mutations in TP53 are associated with low response rates to standard therapy and poor outcomes in patients (pts) with acute myeloid leukemia (AML). Combination therapy with the BCL2 inhibitor venetoclax (VEN) has emerged as an effective treatment option for pts with AML. Methods: We reviewed pts with TP53-mutated AML treated with VEN-based therapy between 2014-2018. Mutation testing was performed using a whole-exome next-generation sequencing panel. We analyzed the characteristics of these pts, responses to therapy, and outcomes. Results: Sixty nine pts with TP53-mutated AML treated with VEN were identified, 36 (52%) in frontline & 33 (48%) in the salvage (R/R) setting (Table). The median follow up was 4.5 [0.5 - 48.5] and 8 [1 - 46.5] months for frontline & R/R pts, respectively. Karyotype was complex in 32 (88%) and 29 (88%) pts in the frontline & R/R cohorts, respectively. In the R/R cohort, the number of median prior treatments was 2 [0 – 8]. VEN was given in combination with: 1) Hypomethylating agents (HMA) (87%), 2) FLAG-Ida (3%), 3) Low dose Ara-C (4%), or 4) CPX-351 (6%). The overall response rate (ORR) was 47% & 24% in frontline and R/R pts, respectively. All 6 pts with negative minimal residual disease (MRD) achieved complete cytogenetic response after taking VEN % remain in complete remission (CR) with a median of 3.4 [1.7-4.7] months. Two pts (both R/R) underwent allogeneic stem cell transplantation. Conclusions: VEN based therapy was associated with similar ORR, but higher CR rates in TP53 mutated AML compared with HMAs alone. Larger studies with longer follow up are needed to determine the role of VEN-based therapy in this difficult subset. Patient characteristics and outcome.