A method was developed for modeling the costs and consequences of treating varicella zoster viral infections to clinical data generated in a pivotal phase III clinical trial of valaciclovir versus acyclovir for the treatment of acute herpes zoster in immunocompetent patients over 50 years of age. Direct medical costs and indirect costs (productivity losses) were modeled using unit costs applicable in the United States. Compared with acyclovir, valaciclovir reduced average direct medical costs per patient by 17% ($60.01) and indirect costs by an average of 25% ($46.54). Median duration of pain was reduced by 13 days for valaciclovir compared with acyclovir in the intent-to-treat population or by 19 days in patients with pain after rash healing. The cost variables described in the model (drug costs, cost of treating long-term pain, physician visits, hospitalization, treatment of severe ocular involvement, productivity losses) were tested by sensitivity analysis. Total costs associated with valaciclovir treatment remained lower than those with acyclovir over the range of the analysis.