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Background: An increasing number of infants are diagnosed with neonatal abstinence syndrome (NAS). The study's primary objectives were to describe an academic medical center's level IV neonatal ICU's (NICU's) comprehensive outpatient NAS management effort, measure guideline compliance, and assess its safety. Secondary objectives were to describe the duration and cumulative methadone exposure, and to improve parent and provider knowledge of NAS., Methods: The study included 22 infants having a gestational age of 35-41 weeks, diagnosed with NAS, and discharged for outpatient methadone management. Discharges spanned 10 months and included 3 improvement periods. The outpatient program includes comprehensive discharge planning, a focused electronic health record (EHR) template, management guidelines, and parent and provider education., Results: Providers complied with using the outpatient management guideline and EHR template, and assessed weight, NAS symptoms, and methadone dose during appointments. Two infants required NAS-related hospital readmission in the study period. From improvement period 1 to period 3 there was no difference in total outpatient days on methadone (58, 53, 74 days, respectively) or cumulative methadone dose (2.7, 2.6, 3.1mg/kg, respectively). A downward trend pattern in cumulative methadone exposure was noted in improvement period 2. Pre- and postimplementation surveys revealed that after implementation, parents had better understanding of NAS before delivery (71% vs. 100%, p = 0.009), while providers had increased comfort with outpatient management (24% vs. 67%, p < 0.001) and educating parents (48% vs. 82%, p = 0.001)., Conclusion: This preliminary study suggests that outpatient NAS management can be safe when a comprehensive management program is implemented and can result in provider compliance with the program., (Copyright 2016 The Joint Commission.)