ObjectiveTo improve care for infants with neonatal abstinence syndrome.DesignInfants with a gestational age of ≥35 weeks with prenatal opioid exposure were eligible for our quality improvement initiative. Interventions in our Plan–Do–Study–Act cycles included physician consensus, re-emphasis on non-pharmacological treatment, the Eat Sleep Console method to measure functional impairment, morphine as needed, clonidine and alternative soothing methods for parental unavailability (volunteer cuddlers and automated sleeper beds). Pre-intervention and post-intervention outcomes were compared.ResultsLength of stay decreased from 31.8 to 10.5 days (p<0.0001) without an increase in readmissions. Composite pharmacotherapy exposure days decreased from 28.7 to 5.5 (p<0.0001). This included reductions in both morphine exposure days (p<0.0001) and clonidine exposure days (p=0.01). Fewer infants required pharmacotherapy (p=0.02).ConclusionsOur study demonstrates how a comprehensive initiative can improve care for infants with neonatal abstinence syndrome in an open-bay or a high-acuity neonatal intensive care unit when rooming-in is not available or other comorbidities are present.