Prescribing of antibiotics for viral upper respiratory infections (URIs) remains a pressing public health problem. We sought to reduce inappropriate prescribing of antibiotics for URIs in Mayo Clinic Arizona. Single-center, quasi-experimental, and retrospective cohort study. Emergency medicine and all primary care departments. The interventions included sharing baseline prescribing data, education, resources, and quarterly peer comparison reports. Encounters with diagnostic codes for respiratory infections commonly caused by viruses were categorized as Tier 3 (ie, never appropriate to prescribe antibiotics). Our goal was to reduce inappropriate prescribing for Tier 3 encounters by 22% in 2022. Department education was completed by June 2022. The annual antibiotic prescribing rate for Tier 3 encounters was reduced by 29%, from a baseline rate of 23.6% in 2021 to 16.4% in 2022 (P < .001). The posteducation prescribing rate was 13.1%. Repeat respiratory-related healthcare contact within 14 days of Tier 3 encounters did not differ between patients prescribed and not prescribed an antibiotic in all of 2022 (4.7% antibiotic vs 4.2% no antibiotic, P = .595) or during the posteducation period (3.7% vs 4.6%, P = .604). A multi-faceted intervention, which included baseline education, syndrome-specific order panels, resources for symptomatic management, and peer comparison reports, resulted in significant reduction of inappropriate antibiotic prescribing for URIs.