BACKGROUND: Streptococcus pneumonia causes invasive diseases as meningitis and bacteremia and non-invasive diseases as pneumonia and acute otitis media (AOM), leading to high morbidity and mortality in infants and the elderly worldwide. OBJECTIVES: To evaluate the cost-effectiveness of universal infant vaccination with 13-valent pneumococcal conjugate vaccine (PCV13) compared with PCV10 in Taiwan. METHODS: A Markov model was developed to evaluate the potential public health and economic impact of PCV13 versus PCV10 when used as routine vaccination of infants in Taiwan with 4 doses at 2, 4, 6, and 12-15 months of age over a 10-year time horizon. We included both direct and potential indirect benefits of the vaccine from societal perspective. Direct effectiveness of PCV13 and PCV10 is estimated from clinical trial data while indirect effectiveness is estimated from U.S. surveillance data. Epidemiology, serotype, medical, and non-medical cost are from Taiwan CDC report, and retrospective Taiwan-population-based insurance database. Other model parameters were captured by published sources, unpublished data, and assumptions made in consultation with clinical experts. Probabilistic sensitivity analyses was performed to test the robustness of model assumptions. RESULTS: At vaccination price (PCV13 cost used current PCV7 price of NT$3,200 (US$ 98) and PCV10 NT$2,700 (US$ 83), our model predicts that, compared to PCV10, universal infant PCV13 vaccination would avoid 2,215 cases of IPD, approximately 12,473 and 14,018 cases of hospitalized and non-hospitalized pneumonia, 246,578 cases of AOM; prevent 207 deaths from IPD and 85 deaths from hospitalized pneumonia; resulting in 4,596 life-years saved, and 3,359 QALYs gained. Comparing PCV13 to PCV10 results in NT$ 187,462 (US$ 5,768 ) per life year saved and cost of NT$ 253,307 (US$ 7,794) per QALY gained from the societal perspective. CONCLUSIONS: Universal pediatric PCV13 vaccination in Taiwan is estimated to reduce the burden of pneumococcal disease and expected to be cost-effective from the societal perspective compared with PCV10.