Objective Antibiotic overuse leading to antimicrobial resistance is a global public health concern. Clinical trials have demonstrated that procalcitonin-based decision-making for antibiotic therapy can safely decrease inappropriate antibiotic use in patients with respiratory infections and sepsis, but real-world data are scarce. This study sought to assess the impact of a procalcitonin-based antibiotic stewardship program (protocol plus education) on antibiotic use in community hospitals. Methods An observational, retrospective, matched cohort study was conducted. Eligible patients treated in hospitals with a procalcitonin-based protocol plus education (Procalcitonin cohort hospitals) were matched to patients admitted to facilities without procalcitonin testing (Control cohort hospitals) using a 1:2 ratio. The Control hospitals were facilities where procalcitonin testing was not available on site. Patient matching was based on: (1) age, (2) gender, (3) admission diagnosis code using groupings of the International Classification of Diseases, 10th Revision, (4) whether patients were admitted to the intensive care unit, and (5) whether a blood culture test was performed. Procalcitonin cohort hospitals implemented a quality improvement initiative, where procalcitonin was available, used regularly, and clinicians (physicians and pharmacists) were educated on its use. Results After adjustment, patients in the Procalcitonin cohort had 1.47 fewer antibiotic days (9.1 vs. 8.5 days, 95%CI: −2.72; −0.22, p = .021). There was no difference in length of stay or adverse clinical outcomes except for increase in acute kidney injury (odds ratio = 1.26, 95%CI: 1.01; 1.58, p = .038). Conclusions Patients with respiratory infections and sepsis in hospitals utilizing a procalcitonin-based protocol coupled with education received fewer days of antibiotic therapy.