Hypomethylating agent (HMA) plus venetoclax (VEN) regimens are standard of care in patients with acute myeloid leukemia (AML) ineligible for intensive chemotherapy. While the VEN label recommends continuous 28-day cycles, shortened VEN durations may induce similar response rates and improve tolerability. It is unknown how a VEN exposure reduced to 7 days during cycles compares to standard HMA + VEN. We retrospectively compared newly diagnosed AML patients treated with azacitidine (AZA) x 7 days plus VEN x 7 days ("7 + 7" regimen) from the first cycle (n = 82) vs patients treated with standard dose HMA + VEN (std-HMA/VEN) (n = 166). Composite complete remission rate was similar between cohorts (72% vs 72%; p = 0.95) and a median number of cycles to best response was 2 with "7 + 7" vs 1 with std-HMA/VEN (p = 0.03). Concerning toxicity, platelet transfusion rates during cycle 1 as well as early mortality at 8-weeks (6% vs 16%; p = 0.03) were lower in "7 + 7" cohort. Finally, the median OS was 11.2 months (2-year 28%) with "7 + 7" vs 10.3 months (2-year 34%) with "std-HMA/VEN" (p = 0.75). In summary, acknowledging limitations of a retrospective comparison, a shortened course of VEN used for 7 days every 28 days resulted in similar response rates and survival when compared to standard VEN exposure.