Background: Published safety data in pregnant epileptic women suggests that oxcarbazepine (OXC) may be a treatment option in nonepileptic pregnant women with substance use disorders (SUDs) and psychiatric symptomatology. Objective: To compare safety outcomes associated with OXC exposure versus non-exposure in nonepileptic pregnant women with SUD and comorbid psychiatric symptomatology. Methods: A retrospective chart review was conducted to identify pregnant women 18 years or older with a SUD who delivered at the study site. Exclusion criteria included a current diagnosis of epilepsy/seizure disorder; concurrent use of lithium, anticonvulsants, medications with a Risk Evaluation and Mitigation Strategy program or a black box warning for potential fetal toxicity; and multi-parity. Eligible patients were divided into two groups based on OXC exposure. Results: The OXC group included 94 mother-neonate pairs versus 194 mother-neonate pairs in the non-OXC group. Baseline characteristics differed in mean number of prior pregnancies (2.8 vs 2.2 in the OXC and non-OXC group, respectively, P = .03). No significant differences were found regarding emergent cesarean or maternal hyponatremia. Average gestational age at OXC initiation was 19.8 weeks. No significant differences were found in the rates of prematurity, physical characteristics, malformation, and neonatal abstinence syndrome. Conclusion: OXC may be considered for management of SUD with comorbid psychiatric symptomatology in nonepileptic pregnant women. Further studies should be conducted to determine statistical significance in larger sample sizes.