Background: We assessed trends in novel cardiovascular medication utilization in US Veterans Affairs (VA) for angiotensin receptor-neprilysin inhibitors (ARNI), sodium-glucose cotransporter-2 Inhibitors (SGLT2i), and glucagon-like peptide-1 receptor agonists (GLP-1 RA)., Methods: We retrospectively identified cohorts from 114 VA hospitals with admission for prevalent 1) systolic heart failure (HF, N = 82,375) or 2) coronary artery disease and diabetes (CAD+T2D, N = 74,209). Site-level data for prevalent filled prescriptions were assessed at hospital admission, discharge, or within 6 months of discharge. Variability among sites was estimated with median odds ratios (mOR), and within-site Pearson correlations of utilization of each medication class were calculated. Site- and patient-level characteristics were compared by high-, mixed-, and low-utilizing sites., Results: ARNI and SGTL2i use for HF increased from <5% to 20% and 21%, respectively, while SGTL2i or GLP-1 RA use for CAD+T2D increased from <5% to 30% from 2017 to 2021. Adjusted mOR and 95% confidence intervals for ARNI, SGTL2i for HF, and SGTL2i or GLP-1 RA for CAD+T2D were 1.73 (1.64-1.91), 1.72 (1.59-1.81), and 1.53 (1.45-1.62), respectively. Utilization of each medication class correlated poorly with use of other novel classes (Pearson <0.38 for all). Higher patient volume, number of beds, and hospital complexity correlated with high-utilizing sites., Conclusions: Utilization of novel medications has increased over time but remains suboptimal for US Veterans with HF and CAD+T2D, with substantial site-level heterogeneity despite a universal medication formulary and low out-of-pocket costs for patients. Future work should include further characterization of hospital- and clinician-level practice patterns to serve as targets to increase implementation., Competing Interests: Disclosures The views expressed in this article are those of the authors and do not necessarily reflect the position or policy of the Department of Veterans Affairs, the U.S. Government, or National Institutes of Health. TS receives support from NHLBI grant 5T32HL007828. HG is supported by Career Development Award Number 1IK2HX002587-01A1 from the United States Department of Veterans Affairs Health Services Research & Development Service of the VA Office of Research and Development. FR reports consulting fees from Novartis, Janssen, NovoNordisk, Amgen, and HealthPals outside the submitted work. SWW has received investigator-initiated research support to the Denver Research Institute from Abiomed, Cardiovascular Systems Incorporated, and Janssen Pharmaceuticals as well as grants from the National Institutes of Health and VA Health Services Research. The remaining authors report no relevant disclosures., (Copyright © 2023. Published by Elsevier Inc.)