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The main objective of this study was to analyze perinatal outcomes of women with substance use disorder in pregnancy who participated in the West Virginia University Medicine Drug Free Moms and Babies Assist Connect and Encourage program (DFMB/ACE) compared to women who were not enrolled in the program. This was a retrospective cohort study conducted in an l Academic Tertiary Care Center. Women who enrolled in DFMB/ACE services from 2018 to 2019 were termed as the intervention group. Their outcomes were compared to 734 women who delivered at the hospital between July 2015 and December 2019 with a positive urine drug screen on admission but were not enrolled in the DFMB/ACE program.Perinatal outcomes evaluated include low birth weight, preterm labor, neonatal intensive care unit (NICU) admission, preterm birth, neonatal abstinence syndrome (NAS), cesarean delivery, cord toxicology result, hepatitis c prevalence, and breastfeeding at the time of discharge. Participants of the DFMB/ACE group had a lower risk of having a preterm birth (OR = 0.56 95% CI 0.36–0.86) compared to the control group. The DFMB/ACE group had higher birth weight compared to the non-DFMB group (2865.7 g. vs. 2657.9 g, p = 0.004). NICU admission, NAS, mode of delivery, cord toxicology, and breastfeeding rates were not statistically different between the two groups. Hepatitis C rates were significantly higher in the intervention vs. non-intervention group (OR = 2.74 95 %CI 1.80 – 4.16). We concluded that the DFMB/ACE program interventions for women with substance use in pregnancy improves some perinatal outcomes for mothers and their newborns.