Introduction Neonatal abstinence syndrome (NAS) is withdrawal syndrome in newborns following birth and is primarily caused by maternal drug use during pregnancy. This study examines trends, population correlates, and policy implications of NAS in two Southwest border states. Materials and Methods A cross-sectional analysis of Hospital Inpatient Discharge Data (HIDD) was utilized to examine the incidence of NAS in the Southwest border states of Arizona (AZ) and New Mexico (NM). All inpatient hospital births in AZ and NM from January 1, 2008 through December 31, 2013 with ICD9-CM codes for NAS (779.5), cocaine (760.72), or narcotics (760.75) were extracted. Results During 2008-2013 there were 1472 NAS cases in AZ and 888 in NM. The overall NAS rate during this period was 2.83 per 1000 births (95% CI 2.68-2.97) in AZ and 5.31 (95% CI 4.96-5.66) in NM. NAS rates increased 157% in AZ and 174% in NM. NAS newborns were more likely to have low birth weight, have respiratory distress, more likely to have feeding difficulties, and more likely to be on state Medicaid insurance. AZ border region (border with Mexico) had NAS rates significantly higher than the state rate (4.06 per 1000 births [95% CI 3.68-4.44] vs. 2.83 [95% CI 2.68-2.97], respectively). In NM, the border region rate (2.09 per 1000 births [95% CI 1.48-2.69]) was significantly lower than the state rate (5.31 [95% CI 4.96-5.66]). Conclusions Despite a dramatic increase in the incidence of NAS in the U.S. and, in particular, the Southwest border states of AZ and NM, there is still scant research on the overall incidence of NAS, its assessment in the southwest border, and associated long-term outcomes. The Healthy Border (HB) 2020 binational initiative of the U.S.-Mexico Border Health Commission is an initiative that addresses several public health priorities that not only include chronic and degenerative diseases, infectious diseases, injury prevention, maternal and child health but also mental health and addiction. The growing opioid epidemic and rise in NAS cases in the Southwest border, as partially shown in this study, provides another opportunity to track health illnesses and outcomes in the Southwest border, especially because there are targeted resources through High Intensity Drug Trafficking Areas (HIDTA) funding.