We examined the cost-effectiveness of the quadrivalent HPV vaccine for the pre-adolescent female population of Brazil. Using demographic, epidemiological and cancer data, we developed a dynamic individual-based model representing the natural history of HPV/cervical cancer as well as the impact of screening and vaccination programmes. Assuming the current screening strategies, we calculated the incremental cost-effectiveness ratio (ICER) for cohorts with and without vaccination taking into account different combinations of vaccination coverage (50%, 70%, 90%) and cost per vaccinated woman (US$25, US$55, US$125, US$556). The results varied from cost-saving (coverage 50% or 70% and cost per vaccinated woman US$25) to 5950 US$/QALY (coverage 90% and cost per vaccinated 556 US$). In a scenario in which a booster shot was needed after 10 years in order to secure lifelong protection, the ICER resulted in 13,576 US$/QALY. Considering the very cost-effective and cost-effective thresholds based on Brazil's GDP per capita, apart from the booster scenario which would be deemed cost-effective, all the other scenarios would be deemed very cost-effective. Both the cost per dose of vaccine and discount rate (5%) had an important impact on the results. Vaccination in addition to the current screening programme is likely to save years of life and, depending on the cost of vaccination, may even save resources. Price negotiations between governments and manufacturers will be paramount in determining that the vaccine not only represents good value for money, but is also affordable in middle-income countries like Brazil.