OBJECTIVES: It is estimated that pneumococcal disease is responsible for more than a million deaths per year in children less than five years of age worldwide. This study aim to perform a cost-effectiveness analysis comparing pneumococcal 13-valent conjugate vaccine (PCV13) against pneumococcal 10-valent conjugate vaccine in prevention of invasive pneumococcal diseases (IPD), acute otitis media (AOM) and pneumonia, from the São Paulo Public Healthcare System perspective. METHODS: The type of study was cost-effectiveness analysis based on a decision tree model to estimate costs and consequences of prophylaxis. Epidemiological and efficacy data was collected from a critical appraisal of the scientific literature, public databases information and clinical expert panel. The target population was a birth cohort in São Paulo followed for 5 years (598,474). The vaccination coverage rate was 90%, considering a four-dose schedule for 10-valent and tree-dose schedule for PCV13 as suggested by international guides. São Paulo costs and disease data was obtained from national official databases. A mandatory discounted price to the government, calculated by the ex-factory price minus 24.38% was considered to PCV13 and 10-valent. Costs and benefits were discounted at 5% annually. Outcomes were expressed as life years gained(LYG), deaths and number of disease cases avoided. Only the direct effect of vaccination and direct medical costs were considered.  RESULTS: The analysis showed higher clinical benefits and lower costs for PCV13 prophylaxis; reduction of 7 deaths, 488 LYG and 17 cases of disease (sepsis and meningitis) and savings of BRL70,097,844(USD43,909,950) in 5 years.  The total costs with events and vaccines were BRL113,902,160(USD72,576,883) and BRL137,914,893(USD87,877,465), respectively, for PCV13; and BRL113,999,789(USD71,410,542) and BRL207,915,109(USD130,239,983) for 10-valent. CONCLUSIONS: This study demonstrated that incorporating PCV13 in pediatric immunization routine results in reduction on mortality and morbidity with lower expected cost for São Paulo state healthcare system, showing the dominance of PCV13 regarding 10-valent.