Background: Antibiotic-resistant bacteria are estimated by the Centers for Disease Control and Prevention (CDC) to kill over 23,000 Americans yearly. Overuse of antibiotics is a leading cause, and reducing unnecessary antibiotic use is a national priority. A major factor in antibiotic overuse is inappropriate or unnecessary culturing, particularly unnecessary urine culturing that identifies colonization and leads to overdiagnosis of urinary tract infections (UTI). Significance/ Impact: Diagnostic stewardship is a novel approach to limiting antibiotic use by modifying the ordering, processing, or reporting of a “positive” culture that generally should not be treated. In preliminary work, we found significant reductions in unnecessary urine cultures and associated antibiotic use through diagnostic stewardship. Diagnostic stewardship is synergistic with antimicrobial stewardship by improving the value and accuracy of urine testing before treatment. This proposal addresses gaps including: Defining best UTI diagnostic stewardship methods, informed by experts and clinicians; developing implementation methods for UTI diagnostic stewardship; and, assessing the impact of real life UTI diagnostic stewardship— both benefits and any harms across acute-care, long-term care, and ambulatory care. This meets HSR&D Research priorities of quality/safety, health care value, cross-cutting HSR methods priorities of implementation science/provider behavior and ORD-wide priority of real-world impact of VA research in addition to national priorities from CDC, Centers for Medicare and Medicaid Services (CMS) and the President’s National Action Plan for Combating Antibiotic-Resistant Bacteria (CARB). Innovation: Modifying how tests are ordered, processed, and reported can help improve patient care by using existing technology more effectively. This is a ‘nudge’ approach, developed from psychology and behavioral economics. This work uses the electronic medical record (EMR) in an innovative, mostly behind the scenes fashion to improve appropriateness of ordering and reporting of tests. A pragmatic proof-of- concept study within an existing network of VA health care systems, using automated outcomes from the VA Corporate Data Warehouse (CDW) is efficient and consistent with the VA goal of being a Learning Health System. Our aims are as follows: Aim 1: Define best UTI diagnostic stewardship criteria, based on literature and Delphi method expert panel. Aim 2: Use iterative user-centered design process to develop EMR interface and lab protocols, with clinicians and other stakeholders (nurses, doctors, technicians, and IT representatives). Aim 3: Conduct a pragmatic proof-of-concept hybrid effectiveness implementation study of the UTI diagnostic stewardship interventions in 3 CDC-CREATE Network Healthcare Systems evaluating benefits and any adverse events. Project Methods: Aims 1 and 2 will use expert panels for developing consensus criteria and a user-centered design process, i...