The COVID-19 pandemic led to numerous measures to mitigate the spread of SARS-CoV-2, including cancellations of gatherings, closure of businesses and schools, social distancing, wearing face masks, and other hygiene measures. 1 These may have unintended positive associations with reducing other respiratory infections. As antibiotics are frequently inappropriately prescribed for viral respiratory diseases, 2 we hypothesized that a decreased respiratory virus incidence would be associated with reduced ambulatory antibiotic orders.Methods | We conducted a pre-post study consisting of a pre-COVID-19 pandemic period (July 2018 to February 2020), a 1-month run-in period (March 2020), and a COVID-19 pandemic period (April 2020 to February 2021). This study received an institutional review board exemption from the University of Wisconsin because it used aggregate prescribing data only, without any patient or clinician identifiers. The Wisconsin State Laboratory of Hygiene provided weekly statewide surveillance polymerase chain reaction data for the following respiratory viruses: influenza, respiratory syncytial virus, human parainfluenza virus, human metapneumovirus, seasonal coronavirus, adenovirus, and enterovirus/ rhinovirus. University of Wisconsin Health is a large, academic health system that serves southern Wisconsin, with more than 80 ambulatory sites and 7 000 000 annual ambulatory encounters. Ambulatory antibiotic prescribing data were collected for all University of Wisconsin Health ambulatory clinics, visit types (eg, in person, telemedicine, and telephone), and ages. We calculated the number of monthly antibiotic prescriptions per 1000 patient encoun-