Purpose: The opioid epidemic is a public health threat with consequences affecting newborns. Neonatal Abstinence Syndrome (NAS) is a constellation of withdrawal symptoms resulting primarily from in utero opioid exposure. The purpose of this study was to examine NAS and drug-specific trends in West Virginia (WV), where rurality-related issues are largely present. Methods: The 2007-2013 WV Health Care Authority, Uniform Billing Data were analyzed for 119,605 newborn admissions with 1,974 NAS diagnoses. NAS (ICD9-CM 779.5) and exposure diagnostic codes for opioids, hallucinogens, and cocaine were utilized as incidence rate (IR) per 1,000 live births. Findings: Between 2007 and 2013, NAS IR significantly increased from 7.74 to 31.56 per 1,000 live births per year (Z: -19.10, P <.0001). During this time period, opioid exposure increased (Z: -9.56, P <.0001), while cocaine exposure decreased (Z: 3.62, P =.0003). In 2013, the southeastern region of the state had the highest NAS IR of 48.76 per 1,000 live births. NAS infants were more likely to experience other clinical conditions, longer hospital stay, and be insured by Medicaid. Conclusions: Statewide NAS IR increased 4-fold over the study period, with rates over 3 times the national annual averages. This alarming trend is deleterious for the health of WV mother-child dyads and it strains the state's health care system. Therefore, WV has a unique need for prenatal public health drug treatment and prevention resources, specifically targeting the southeastern region. Further examination of maternal drug-specific trends and general underutilization of neonatal exposure ICD-9-CM codes is indicated.