OBJECTIVES: Streptococcus pneumonia causes invasive pneumococcal diseases (IPD), meningitis and bacteremia, and non-invasive diseases such as pneumonia and acute otitis media (AOM), leading to high morbidity and mortality in infants and elderly in Malaysia. To examine the health and economic impacts of routinely vaccinating infants with 13-valent pneumococcal vaccine (PCV13) compared to 10-valent pneumococcal conjugate vaccine (PCV10) or no vaccine in Malaysia.METHODS: A Markov model was adapted with local data to evaluate the potential public health and economic impact of routine vaccination of infants with PCV10 or PCV13 over a 10-year time horizon, assuming a 3-dose regimen at 2, 4, 12 months of age and coverage of 90%. Direct effectiveness of PCV13 and PCV10 was estimated from clinical trial data while indirect (herd) effectiveness was estimated from U.S. surveillance data. Epidemiology, serotype coverage, and costs were from published studies and government websites. One-way and multivariate probabilistic sensitivity analyses were performed to test the robustness of model assumptions.RESULTS: Compared to no vaccination, universal infant PCV13 vaccination would avoid 19,833 cases of IPD, 832,687 and 1,705,984 cases of hospitalized and non-hospitalized pneumonia respectively, and 135,675 cases of AOM with the prevention of 4,531 deaths from IPD and 34,648 deaths from hospitalized pneumonia over 10 years. Compared to no vaccination, PCV13 vaccination would be cost-effective at RM21,998 per QALY gained from the societal perspective.  Compared to PCV10, PCV13 vaccination would avoid an additional 9,651 cases of IPD, 392,684 and 980,434 cases of hospitalized and non-hospitalized pneumonia respectively, and 81,118 cases of AOM with the prevention of 18,736 deaths. Compared to PCV10, PCV13 vaccination would be cost-effective at RM6,315 per QALY gained. CONCLUSIONS: Universal pediatric PCV13 vaccination in Malaysia was estimated to reduce the burden of pneumococcal diseases and is expected to be cost-effective compared with both no vaccination and PCV10.