OBJECTIVES: Invasive pneumococcal disease (IPD) is a major public health challenge. Pediatric high-risk population (PHR) (like sickle cell disease, HIV infected or those receiving immunosuppressive medications) are 30-100 times more likely to develop IPD compared to healthy children. This study aims to perform cost-effectiveness analysis of 13-valent pneumococcal vaccine (PCV13) in PHR, from a public payer perspective in Brazil. METHODS: A decision tree-model was developed to simulate IPD outcomes in PHR after vaccination with PCV13 versus PCV10 and non-vaccination and their associated direct costs in a 10-year time horizon. Despite comparison with PCV10, this indication is off-label in Brazil and no studies are available to this population segment. Effectiveness parameters are avoided cases of IPD, hospitalized and non-hospitalized pneumonia. Direct medical costs included hospital days, medical personnel time, outpatient visits, diagnostic tests and medications. Clinical data and costs were extracted from literature, presented in 2012 USD. Probabilistic sensitivity analyses were performed trough Monte Carlo Simulation second-order approach. RESULTS: For a 611,737 patients cohort, PCV13 avoided [1,626; 1,851] IPD, [1,996; 92,805] hospitalized pneumonia, [1,585; 73,700] non-hospitalized pneumonia, and [570; 649] IPD deaths, versus [PCV10; non-vaccination]. Projected treatment costs for PCV13 versus PCV10 were 703,326,000USD, and 707,410,000USD, respectively. For PCV13 versus non-vaccination projected treatment costs was 367,000,000USD versus 705,000,000USD, respectively. In cost-effectiveness analysis, PCV13 was cost-saving in all comparisons. CONCLUSIONS: From the public payer perspective in Brazil, PCV13 showed to be dominant regarding life years gained than PCV10 vaccination and non-vaccination strategy.