OBJECTIVES: The quadrivalent (6,11,16,18) HPV vaccine has been approved in Brazil for prevention of cervical cancer, vulvar/vaginal pre-cancers, and genital warts in women age 9 to 26 years.  We assessed the health and economic impact of the quadrivalent (6,11,16,18) HPV vaccine from the healthcare system perspective in Brazil. METHODS: A published mathematical model of the transmission dynamics of HPV infection and disease was adapted for Brazil.  Model inputs were used from Brazil or the Latin/America region when available; otherwise, the default values in the original model were used. Maintaining current cervical cancer screening practices in Brazil, we evaluated two strategies: routine vaccination of females by age 12 (S1), and S1 combined with a temporary (5 years) female catch-up program for age 12–24 years (S2).  The vaccine coverage rates were 85% for the routine and 50% for the catch-up vaccination programs.  RESULTS: The most effective strategy was S2.  Comparing S2 to no vaccination, we estimated the cumulative percent reduction in incident HPV 6/11/16/18-related genital warts-female, genital warts-male, cervical intraepithelial neoplasia (CIN) grade 1,  CIN 2/3 , and cervical cancer cases would be 81%, 57%, 70%, 72%, and 59%, respectively over 100 years.  The cost-effectiveness ratios were Brazil Reals 1,203 (US$ 699) per quality-adjusted life years (QALY) gained for S1 compared with no vaccination, and Brazil Reals 1,522 (US$ 885) per QALY gained for S2 compared with S1. CONCLUSIONS: In Brazil, vaccination of females age 12–24 years with a quadrivalent (6,11,16,18) HPV vaccine can reduce the incidence of cervical cancer, CIN, and genital warts at a cost per QALY ratio within the range typically regarded by the World Health Organization as cost-effective.