Ambulatory antimicrobial stewardship can be challenging due to disparities in resource allocation across the care continuum, competing priorities for ambulatory prescribers, ineffective communication strategies, and lack of incentive to prioritize antimicrobial stewardship program (ASP) initiatives. Efforts to monitor and compare outpatient antibiotic usage metrics have been implemented through quality measures (QM). Healthcare Effectiveness Data and Information Set (HEDIS®) represent standardized measures that examine the quality of antibiotic prescribing by region and across insurance health plans. Health systems with affiliated emergency departments and ambulatory clinics contribute patient data for HEDIS measure assessment and are directly related to value-based reimbursement, pay-for-performance, patient satisfaction measures, and payor incentives and rewards. There are four HEDIS® measures related to optimal antibiotic prescribing in upper respiratory tract diseases that ambulatory ASPs can leverage to develop and measure effective interventions while maintaining buy-in from providers: avoidance of antibiotic treatment for acute bronchitis/bronchiolitis, appropriate treatment for upper respiratory infection, appropriate testing for pharyngitis, and antibiotic utilization for respiratory conditions. Additionally, there are other QM assessed by the Centers for Medicare and Medicaid Services (CMS), including overuse of antibiotics for adult sinusitis. Ambulatory ASPs with limited resources should leverage HEDIS® to implement and measure successful interventions due to their pay-for-performance nature. The purpose of this review is to outline the HEDIS® measures related to infectious diseases in ambulatory care settings. This review also examines the barriers and enablers in ambulatory ASPs which play a crucial role in promoting responsible antibiotic use and the efforts to optimize patient outcomes.