BackgroundUrgent care medicine is a rapidly growing health care sector where patients are commonly treated for acute infectious diseases–related conditions. However, there are few antimicrobial stewardship interventions described in these settings. ObjectiveThe objective of this study is to determine whether implementing outpatient antimicrobial stewardship guidelines would improve antibiotic prescribing for acute upper respiratory tract infections (ARTIs), skin and soft tissue infections (SSTI), and urinary tract infections (UTI) at a single urgent care site. MethodsThis was a pre-post interventional study comparing antibiotic prescribing patterns for ARTI, SSTI, and UTI at a single urgent care site in the preintervention group (November 2019 to January 2020) with the postintervention group (November 2020 to January 2021) after implementation of outpatient stewardship guidelines. A second urgent care site that did not receive any interventions served as a control. The outpatient stewardship guidelines were implemented in October 2020 via didactic provider education and pocket guide distribution. The primary end point was the rate of total guideline-concordant antibiotic prescribing. Secondary end points included the rates of guideline concordance of each component of the prescription, including antibiotic selection, duration, dose, therapy indication, and patient safety outcomes. ResultsThe primary outcome of total guideline-concordant antibiotic prescribing significantly improved after implementation of outpatient antimicrobial stewardship guidelines at the study site (50% vs. 70%, P < 0.001), which was also reflected when comparing postintervention study site with postperiod control site (70% vs. 48%, P < 0.001). There was a statistically significant improvement in guideline-concordant duration of antibiotic therapy (43% vs. 61%, P = 0.001), driven by a reduction in antibiotic duration for UTI (7 [interquartile range (IQR) 5–7] vs. 5 [IQR 5–7] days, P = 0.007), which was also observed when comparing the postintervention study site with the postperiod control site (61% vs. 48%, P = 0.02). Patient safety outcomes were similar between groups. ConclusionAn antimicrobial stewardship intervention comprising institutional outpatient guideline implementation and provider education significantly improved total guideline-concordant antibiotic prescribing by 20% for ARTI, UTI, and SSTI in an urgent care site.