Decision analysis was used in the evaluation of nine strategies for the prevention of neonatal infection with herpes simplex virus (HSV). These strategies involve physical examination at labor, weekly screening of pregnant women for shedding of HSV, use of serologic methods specific for HSV type 2, and performance of a rapid diagnostic test at labor. Rates of cesarean delivery and of neonatal infection with HSV were estimated for each strategy, and the estimates were compared with those for a strategy of no intervention. The effects of variations in the sensitivities and specificities of the diagnostic and serologic tests used were analyzed. Given the currently available data and technology, physical examination at labor is the optimal strategy if the primary goal is to minimize the ratio of excess cesarean sections to cases of neonatal HSV infection averted.