OBJECTIVES: This study estimates the cost and the effectiveness of brivudine and aciclovir in the treatment of Herpes Zoster (HZ) in Spain focusing on the number of post herpetic neuralgia (PHN) avoided cases. METHODS: A cost-effectiveness decision model was built from clinical results obtained in the double-blind controlled trail that compared brivudine and aciclovir. The analytic model estimates the mean cost per patient treated with HZ and the mean cost per PHN avoided case. Time horizon of the study considered HZ acute treatment period (7 days) plus PHN treatment period (between 90 and 180 days). This decision model also considers the incidence rate of HZ in Spain for patients older than 50 years, clinical drug effectiveness, HZ and PHN direct medical costs and three PHN treatments options (tramadol, gabapentine and pregabaline). RESULTS: It has been estimated that 109.982 patients with HZ would be treated in Spain each year. If all those patients would be treated with brivudine, then 8,976 NPH cases could be avoided if the same number of patients would receive aciclovir. Mean cost per treated patient would be lower with brivudine for all PHN treatment options. Overall, brivudine has a greater effectiveness and a lower cost per treated patient, thus estimated direct medical cost per PHN avoided case would be reduced in 33€ when the PHN patient is treated with tramadol, 35€ for gabapentine and 71€ for pregabaline. CONCLUSION: Results from base-case and sensitivity analysis indicate that brivudine is a cost-effective treatment for HZ when it is compared to aciclovir in the Spanish setting.