BACKGROUND: Since 2006, Dutch children receive a 7-valent pneumococcal conjugate vaccine (PCV7) against Streptococcus pneumoniae (pneumococci), a leading cause of childhood illnesses. New vaccines, covering a wider range of serotypes, will soon be available. OBJECTIVES: To evaluate the cost-effectiveness of 10- and 13-valent vaccines (PCV10 and PCV13) by calculating quality adjusted life years (QALY) and costs, and estimate the cost-utility from the societal perspective. METHODS: A Markov model was used to calculate the effects of vaccinating a single cohort of newborn children in terms of two non-invasive diseases (pneumonia, acute otitis media) and two invasive diseases (meningitis, bacteremia) with associated sequelae and mortality. Vaccination effectiveness was estimated using trial data. Scenario analysis was conducted to analyze the effects of herd immunity. Probabilistic sensitivity analysis was carried out on incidences, costs, transition probabilities, utility weights and vaccine effectiveness. RESULTS: Assuming equal price per dose, both PCV10 and PCV13 were dominant compared to PCV7, with lower costs and more QALYs. Due to the larger range of serotypes, PCV13 has the fewest cases of pneumonia, invasive diseases and sequelae, and is the most cost-effective treatment, dominant to both other treatments. However, the superior effectiveness of PCV10 against the very prolific otitis compensates in such a way that the difference in both costs and QALYs between PCV10 and PCV13 is much smaller than was expected beforehand. CONCLUSIONS: From a cost-utility perspective, PCV7 could be replaced by either one of the new vaccines, when they become available. The choice between PCV10 and PCV13 will depend primarily on price setting and the importance that is assigned to indirect costs. PCV10 prevents more cases of frequent, but cheaper otitis, PCV13 prevents more cases of less frequent, but more costly in both money and effects, invasive diseases.