OBJECTIVES: To describe incidence, health care use, and cost trends for infants with neonatal abstinence syndrome (NAS) who are covered by Medicaid compared with other infants. METHODS: We used 2004–2014 hospital birth data from the National Inpatient Sample, a nationally representative sample of hospital discharges in the United States (N = 13 102 793). Characteristics and trends among births impacted by NAS were examined by using univariate statistics and logistic regression. RESULTS: Medicaid covered 73.7% of NAS-related births in 2004 (95% confidence interval [CI], 68.9%–77.9%) and 82.0% of NAS-related births in 2014 (95% CI, 80.5%–83.5%). Among infants covered by Medicaid, NAS incidence increased more than fivefold during our study period, from 2.8 per 1000 births (95% CI, 2.1–3.6) in 2004 to 14.4 per 1000 births (95% CI, 12.9–15.8) in 2014. Infants with NAS who were covered by Medicaid were significantly more likely to be transferred to another hospital and have a longer length of stay than infants without NAS who were enrolled in Medicaid or infants with NAS who were covered by private insurance. Adjusting for inflation, total hospital costs for NAS births that were covered by Medicaid increased from $65.4 million in 2004 to $462 million in 2014. The proportion of neonatal hospital costs due to NAS increased from 1.6% in 2004 to 6.7% in 2014 among births that were covered by Medicaid. CONCLUSIONS: The number of Medicaid-financed births that are impacted by NAS has risen substantially and totaled $462 million in hospital costs in 2014. Improving affordable health insurance coverage for low-income women before pregnancy would expand access to substance use disorder treatment and could reduce NAS-related morbidity and costs.