Abstract: Objective:: Inpatient antibiotic use increased during the early phases of the COVID-19 pandemic. We sought to determine whether these changes persisted in persons with and without COVID-19 infection. Design:: Retrospective cohort analysis. Setting:: 108 Veterans Affairs (VA) facilities. Patients:: Persons receiving acute inpatient care from January 2016 to October 2022. Methods:: Data on antibacterial use, patient days present, and COVID-19 care were extracted from the VA Corporate Data Warehouse. Days of therapy (DOT) per 1000 days present (DP) were calculated and stratified by Centers for Disease Control and Prevention-defined antibiotic classes. Results:: Antibiotic use increased from 534 DOT/1000 DP in 11/2019–2/2020 to 588 DOT/1000 DP in 3/2020–4/2020. Subsequently, antibiotic use decreased such that total DOT/1000 DP was 2% less in 2020 as a whole than in 2019. Driven by treatment for community acquired pneumonia, antibiotic use was 30% higher in persons with COVID-19 than in uninfected persons in 3/2020–4/2020, but only 4% higher for the remainder of 2020. In 2022 system-wide antibiotic use was 9% less in persons with COVID-19; however, antibiotic use remained higher in persons with COVID-19 in 25% of facilities. Discussion:: Although antibiotic use increased during the early phases of the COVID-19 pandemic, overall use subsequently decreased to below previous baseline levels and, in 2022, was less in persons with COVID-19 than in persons without COVID-19. However, further work needs to be done to address variances across facilities and to determine whether current levels of antibiotic use in persons with COVID-19 are justified.