PROJECT SUMMARY/ABSTRACT Opioid misuse and overdose remain a major public health crisis in the United States, especially for youth.1,2 In 2022, more than 110,000 people died from opioid overdoses.3 While the rate of intentional drug overdoses fell among middle-aged adults from 2015-2019, it rose among youth aged 15-24.2 Rates of opioid overdose increased for all age groups in 2020 and 2021, with the largest increases among adolescents in both years.4 Approximately 4 million children and adolescents (age 0-17) undergo surgical procedures every year in the United States,5 which present a first exposure to opioids for many and may become a driver of future opioid use disorders (OUD) in this vulnerable age group.6–9 This project aims to confront an important aspect of the national opioid crisis by providing greater insight into OUD risk after initial opioid exposure in the surgical setting during adolescence. The proposed study will lay the groundwork for the development of better and safer pain management strategies for adolescents undergoing major surgery and will inform guidelines for opioid prescribing to adolescents by establishing a multicenter prospective, cohort. We will investigate the impacts of individual sociodemographic and clinical characteristics, intra-operative factors, and postoperative surgical course on the development of markers of elevated risk for OUD. Outcomes of interest include prolonged opioid use after surgery and postoperative non- medical use of prescription opioids (NMUPO) which are risk factors for subsequent OUD in this vulnerable adolescent population. We will recruit a diverse sample of 10,000 adolescents (aged 12 to 17 years) undergoing a painful surgical procedure. We will survey patients and parents preoperatively and at 5 time points up to 12 months post- operatively to understand patient experiences of pain and related patient reported outcomes. Survey data will be combined with structured clinical pre- intra- and post-operative data abstracted from the electronic medical record to characterize the inter-relationships among patient experiences, behaviors, and clinical course. Our findings could revolutionize post-operative pain care for this vulnerable population. Results will inform screening and assessment of OUD risk prior to opioid prescribing, strategies for reducing OUD risks for those undergoing painful procedures, and recommendations for monitoring of patients being treated for pain. Additionally, the project enables the establishment of an infrastructure among pediatric surgical centers that can be used for future projects to further evaluate best practices for securing favorable post-operative outcomes for youth.