Background Newborn opioid dependence is increasing due to rising opioid addiction among childbearing-aged women. Newborns often suffer effects before treatment. To prevent severe symptoms in high-risk newborns, an innovative early treatment model (MAIN) was developed. The study objective was to describe this model and report medical, safety and healthcare utilization outcomes. Methods A retrospective chart review was conducted for Neonatal Abstinence Syndrome (NAS) infants (ICD-9 codes 760.72, 779.5) born in a large regional hospital from 2006-2014 and treated with the MAIN model in a Level I nursery. Primary outcomes were length of stay, adjunctive medication use, safety/adverse events, emergency visits and readmission rates, and total hospital costs and charges. Outcomes were compared to national and state data. Results 117 newborns were treated using the MAIN model. Mean length of stay was eight days versus 12 days statewide. Two percent needed adjunctive medication; four percent experienced oversedation. Eleven hospital safety events occurred, including drops and unsafe sleep practices. There were no medication errors or deaths. Within 30 days of discharge, 14% visited the emergency department; 7% were readmitted, largely for reasons unrelated to NAS. Mean hospital charges were $10,171.52 compared to $43,469.42 per NAS birth statewide. Conclusions This study is the first to describe an early treatment model to prevent severe NAS. Our data demonstrate that the model may be safe, effective, low-cost, and feasible for replication. With further study, it may have widespread applicability and contribute to improving clinical outcomes for newborns at high risk for opioid withdrawal.