OBJECTIVE: To determine the incidence of possible neonatal herpes simplex virus (HSV) infections, HSV infection status of women with infected infants, and use of measures to reduce risk of HSV transmission to the neonate in a large US managed-care population. STUDY DESIGN: Retrospective analysis of administrative claims from the Integrated Health Care Information Services National Managed Care Benchmark database. RESULTS: Of 233,487 infants born to 252,474 mothers from January 1997 to June 2002, the numbers assigned an ICD-9 code reflecting possible neonatal HSV infection ≤30 and ≤90 days of birth were 178 (0.08%) and 338 (0.15%), respectively. Of the 338 mothers delivering infants with possible neonatal HSV ≤90 days postnatally, 12% had a prior HSV diagnosis, 5% were prescribed an antiviral medication during the study period, and 3% used antiviral medication and had a cesarean delivery. CONCLUSION: These results support national surveillance of neonatal HSV to better define its incidence, strengthen health policies, and improve prevention and treatment. © Copyright 2007 American Sexually Transmitted Diseases Association.