Background: AML is an aggressive hematologic malignancy of older adults (median age at diagnosis: 68 y); median overall survival (mOS) is low, even with Tx. The VIALE-A study changed the standard of care by combining venetoclax (VEN) with a hypomethylating agent (HMA), extending mOS from 9 to 14 mo. With the evolving Tx landscape and growing availability of less-intensive induction chemotherapy (IC), it is important to understand the impact of these Tx in the real world. This study evaluated Tx patterns and clinical outcomes for patients (pts) with AML who received intensive IC, VEN-based Tx (eg, VEN + azacitidine), or non-VEN-based low-intensity (NVB-LI) Tx (eg, a single HMA) in the first-line (1L) setting. Methods: A retrospective, observational, US-based, cohort study was conducted utilizing electronic health record data from adults with AML who initiated 1L IC between 01/01/2016 and 12/31/2019, or 1L VEN-based Tx or 1L NVB-LI Tx between 01/01/2019 and 12/31/2020. Eligible pts had ≥6 mo of follow-up after 1L initiation (or <6 mo due to death). Pts who received AML Tx as part of clinical trials were excluded. Remission was defined as a physician-reported best response of complete remission (CR), CR with incomplete hematologic improvement, or CR with no measurable residual disease. Time-to-event outcomes were assessed using the Kaplan–Meier method; all other data were summarized using descriptive statistics. Results: A total of 451 pts were included; 54% were male, 70% were White. Median follow-up was 17 mos. Mean age at 1L initiation was 52, 73, and 76 y in the IC, VEN, and NVB-LI cohorts, respectively. Among the 207 pts in the IC cohort, 99% discontinued Tx during follow-up, 85% of whom discontinued due to completion of Tx. Among the 152 pts in the VEN cohort and 92 in the NVB-LI cohort, 72% and 75% discontinued Tx, respectively, primarily due to disease progression (59% and 68% of discontinuing pts, respectively). Median duration of 1L Tx was 2, 11, and 7 mo in the IC, VEN and NVB-LI cohorts, respectively. In the IC, VEN, and NVB-LI cohorts, 80%, 45%, and 20% of pts achieved remission during 1L Tx; median time to remission was 1, 3, and 3 mo, respectively. Median relapse-free survival was not reached during follow-up in any of the cohorts. In the IC cohort mOS was not reached; mOS was 17 mo in the VEN cohort, and 9 mo in the NVB-LI cohort. Conclusions: Pts receiving 1L IC had the highest rate of remission, the shortest time to remission, and the most favorable mOS among all Tx cohorts, supporting continued intensive chemotherapeutic approaches with curative intent in eligible pts. mOS favored combination VEN-based Tx over NVB-LI, suggesting that VEN-based therapies may provide more benefit for pts ineligible for IC. Further research is warranted to determine the most appropriate Tx approach for pts with AML based on Tx effectiveness, pt medical history, and IC eligibility.