OBJECTIVES: Genital herpes affects more than 45 million individuals in the United States with an estimated 400,000 physician office visits each year for primary infections. With no cure for the herpes infection, it can be transmitted from the infected individuals to the unsuspecting population throughout the lifetime of the infected. With the approaching patent expiration for the prescription drug valacyclovir (Valtrex®) in 2009, this study examines the implications of transitioning valacyclovir to an over the counter (OTC) status. METHODS: A decision analysis model was used to examine the current prescription based requirement for valacyclovir compared to the OTC status for the product. The analysis was constructed from a societal perspective using a budget impact model. A simulation model conducted in a hypothetical cohort of 10,000 individuals with primary genital herpes in the United States with direct medical cost as the principal outcome. Cost estimations are based on literature review and national healthcare databases. A sensitivity analysis through a Monte Carlo simulation will assess the validity of the cost estimates. RESULTS: The transition of valacyclovir to OTC status will amount to an average annual savings of $707 ($544-$868) per newly infected individual in the form of direct medical expenditures. The annual average cost for the OTC transition is $108 per newly infected, compared to the annual average cost of the prescription based requirement of $815 per newly infected. Aggregate annual savings to the United States from newly infected individuals is $282 million per year. CONCLUSIONS: Transitioning valacyclovir to OTC status is a cost saving measure for society, largely due to the decrease in physician office visits for valacyclovir prescriptions. Further studies will need to address specific population needs in regards to herpes education, feasibility of self-diagnosis, viral resistance and indirect cost.