An evidence-based, multidisciplinary neonatal abstinence syndrome protocol was developed using a stepwise continuous quality improvement (CQI) approach with the goal of standardizing care procedures for these infants. A retrospective secondary data analysis was performed to evaluate the differential effects of each step of the CQI project on 4 key clinical outcome measures: length of stay (total and post–opioid wean), weaning time from opioids, and use of adjunct medications. Data were analyzed from 386 newborn infants with a diagnosis of neonatal abstinence syndrome undergoing treatment in a level III neonatal intensive care unit. After implementation of a pharmacologic weaning protocol as a foundational first step of the CQI project, the weaning time from opioids remained stable throughout each of the subsequent CQI steps (P = .905). The overall total neonatal intensive care unit length of stay was reduced by 10.35 days (P = .002), and the length of neonatal intensive care unit stay after completing wean from opioids was reduced by 2.79 days (P < .001). Use of adjunct medications also decreased from 30.1% of infants at the initiation of the CQI project to 24.5% at the completion of the project (P = .020). These findings indicate that this multidisciplinary treatment approach led to an overall improved efficiency of both opioid weaning and symptom management for these infants.