Background: Antimicrobial overuse is one of the strongest risk factors for the emergence of antimicrobial resistance, an urgent public health problem. Antimicrobial stewardship programs (ASPs) are hospital-based programs that can reduce unnecessary inpatient antimicrobial use and are therefore an essential tool for addressing the crisis of antimicrobial resistance. ASPs are mandated in VHA. Significance: VHA hospitals are only required to monitor their inpatient antimicrobial use. However, at least 40% of antimicrobial exposure associated with a VHA hospital stay is prescribed at hospital discharge and is taken by the patient after discharge (i.e. post-discharge). These post-discharge antimicrobial prescriptions are frequently unnecessary or sub-optimal. Reducing post-discharge antimicrobial overuse will minimize patient harm, such as Clostridioides difficile infections, antimicrobial resistance, and adverse drug events. Innovation and Impact: This proposal will address two critical gaps in the literature. First, standard ASP metrics do not capture post-discharge antimicrobial use and therefore miss a substantial amount of hospital- related antimicrobial exposure. This proposal will evaluate factors that contribute to variation in post-discharge antimicrobial use across patients and hospitals in order to inform both metric development and the design of future stewardship interventions. Second, while there are evidence-based strategies for safely reducing inpatient antimicrobial use, it is unclear how current inpatient ASP activities can decrease post-discharge antimicrobial overuse. This proposal will explore how inpatient ASP infrastructure, which all VHA hospitals are expected to have, can be leveraged to reduce unnecessary post-discharge antimicrobial-prescribing. Specific Aims: Aim 1: Identify factors that contribute to variation in post-discharge antimicrobial use in VHA acute-care admissions across all facilities by evaluating potential patient-level, hospital-level, and environmental effects. Identify hospitals that have low observed-to-expected post-discharge antimicrobial use, low risk-adjusted inpatient antimicrobial use, and perform well on clinical outcomes in antimicrobial-treated patients. Aim 2: Determine whether being admitted to a hospital with a discharge-focused stewardship process is associated with less post-discharge antimicrobial exposure, after adjusting for differences in case-mix, ID expertise, inpatient antimicrobial exposure, and the intensity of inpatient ASP activities. Aim 3: Using qualitative methods, evaluate attitudes and processes that impede or foster reductions in unnecessary post-discharge antimicrobial use. We will perform site visits at 6 high- and 4 low-performing sites, as identified in Aim 1. Methodology: Aim 1 will use VINCI data and linear mixed models to identify factors that influence post- discharge antimicrobial use. Aim 1 will also rank hospitals on their performance on inpatient and post- dischar...