Key PointsQuestionWhat is the association between a multifaceted antibiotic stewardship initiative with antibiotic prescribing for respiratory conditions in a large urgent care (UC) network?FindingsThis quality improvement study of 493 724 total UC encounters found a decrease in antibiotic prescribing for respiratory conditions from 48% (baseline) to 33% (intervention), with reductions of 22% at the start of the intervention and 5% per month throughout the 1-year intervention period.MeaningThis study’s findings suggest that a multifaceted antibiotic stewardship initiative was associated with reduced antibiotic prescribing for UC respiratory conditions, and that such initiatives in large UC networks may decrease inappropriate antibiotic prescribing.