OBJECTIVES: To evaluate the health and economic impact of the expansion of YF virus in Brazil in the period of 2000-2009. METHODS: The perspective of study was the public health care system. We evaluated the direct costs of hospitalization and YF vaccine. Data source was the public official national information on YF cases and YF vaccination from Brazilian Ministry of Health. We assumed that all cases required hospitalization and that all fatalities required intensive care unit (ICU) hospitalization and dialysis. All values were referent to December of 2009. The values of hospitalization by yellow fever, five days ICU hospitalization and five days dialysis paid by public health system were, respectively, R$174.45 (€79.3); R$2393.60 (€1088) and R$ 557.1 (€253.23). RESULTS: During the evaluated period, YF virus circulation was detected in eight states previously YF free. There were 320 cases of YF with lethality rate of 46.5%. The cumulative population vaccinated was 90,906,675 individuals. The YF related hospitalization cost was R$ 495,478.30 (€225,217.41) and YF vaccine cost was R$89,997,608 (€40,908,003.75) within the 10 year period evaluated. CONCLUSIONS: Even in areas with susceptive population there were few cases of yellow fever. However, the significant clinical impact of the disease was due to its high lethality. Despite the severity of yellow fever, hospitalization costs were modest in the study period. The main cost was with the vaccine, the only form of prevention and control of disease. Thereby, it is necessary to evaluate the financial impact of vaccinating the areas that still have no evidence of the yellow fever virus, since there seems to be an expansion tendency of YF virus circulation to the country as a whole and the vaccination could prevent YF cases and deaths.