The objective of the study was to assess varicella epidemiology and the cost of disease in Spain, in order to perform a cost benefit analysis of universal vaccination at 15 months of age. Epidemiological data were obtained from a survey of 150 children with varicella, from hospitalizations and from the Spanish literature. A Markov decision tree was designed with two alternatives, vaccination or nonvaccination. Direct costs derived from the disease were lower than the cost of vaccination (ratio 0.54:1), however when indirect costs, such as working time loss were taken into account, vaccination was the best alternative, with a saving of P(T)2627 per vaccinated subject (P(T)1.6 recovered per peseta invested in the program). Sensitivity analysis shows that decreasing vaccine coverage and efficacy to 0.7, increasing the annual discount rate to 20% and with a vaccine price less than P(T)6000, vaccination is always the best alternative. In conclusion, from the economic point of view, a universal varicella vaccination program in children at 15 months of age would be justified in Spain.