ABSTRACT Opioid use, diagnoses of opioid use disorder among pregnant women, and diagnoses of neonatal opioid withdrawal syndrome (NOWS) increased dramatically over the past 20 years. In 2017, an estimated 100,000 infants were exposed to opioids, among whom 25,000 infants were diagnosed with NOWS. Opioid-exposed infants, regardless of whether they are diagnosed with NOWS, are more likely to have adverse outcomes compared to similar non-exposed infants, including: longer and more complicated initial hospital stays, higher likelihood of involvement in the child welfare system, higher rates of hospital readmission and emergency department visits and lower use of recommended preventive services. Further, delivery of medical care to opioid-exposed infants remains variable resulting in uneven outcomes among US hospitals and communities. The development of valid and reliable measures for opioid-exposed infants is critical to improving outcomes for this vulnerable population. To fill this existing gap we will: 1) develop candidate measures of quality for opioid- exposed infants and refine these measures by engaging key stakeholders including local, state, and national public policy makers; private and public insurers; health care providers; and families using a modified RAND/UCLA Appropriateness Method; 2) determine the reliability, reproducibility and validity of measures of candidate quality measures while evaluating the usability, validity, and reliability of the measures using two unique sets of data, linked maternal-infant data from the Medicaid Analytic Extract from 2007-2014 and clinically collected data from two large clinical systems and will determine risk-adjusted hospital variation in measures for opioid-exposed infants in a large population-based sample. This R34 will produce quality measures for opioid-exposed infants and preliminary data that will subsequently inform an R01 pragmatic clinical trial that will evaluate how clinician performance on quality measures results in changes to provider behaviors and subsequent alterations in infant outcomes. In addition, these measures can also serve as the outcomes for randomized clinical trials that examine the impact of various treatments on the health and wellbeing of opioid-exposed infants and whether they experience withdrawal symptoms after birth. The ultimate goal of this R34 and subsequent R01s will be to provide innovative tools for clinicians, researchers, policymakers, payers, hospital systems and state perinatal collaboratives to improve care for opioid-exposed infants.