OBJECTIVES: To evaluate cost-effectiveness of routine pneumococcal vaccination with 10-valent pneumococcal non-typeable Haemophilus influenzae protein-D vaccine (PHiD-CV) compared with 13-valent pneumococcal conjugate vaccine (PCV-13) and no vaccination. METHODS: A Markov cohort model with a 100-year time horizon was developed to project the impact of vaccination on the incidence of pneumococcal and non-typeable Haemophilus Influenzae (NTHi) infections in children and adults. Data Sources: Czech Republic-specific epidemiological and demographic data and data from other country sources. Base case assumptions include estimates of pneumococcal and NTHi infection rates as well as vaccine efficacy based on published literature. Model inputs: payer perspective, 80% vaccine coverage, no herd protection and a (3+1) vaccination schedule. One-way sensitivity analyses performed to assess the impact of changes in key model assumptions.  RESULTS: PHiD-CV and PCV-13 are projected to prevent more cases of invasive disease (89 and 92 respectively) and pneumonia hospitalizations (738 and 760 respectively) compared with no vaccination. PHiD-CV and PCV-13 are projected to prevent additional GPP/ENT visits due to acute otitis media (AOM) (7851 and 3838 respectively) compared with no vaccination strategy. The total number of cases of invasive disease was comparable for both vaccines but PHiD-CV is estimated to prevent more than 14 000 cases of AOM in comparison with  PCV-13. Vaccinating a birth cohort with PHiD-CV is expected to generate 75.5 more QALYs and 5.9 LYG compared to PCV-13. Under vaccine price parity assumptions, estimated total savings for healthcare system are 10.2 mil CZK or 395.6 k EUR for PHiD-CV compared to PCV-13 respectively. Sensitivity analyses indicate that AOM efficacy and incidence of AOM related GPP/ENT visits have biggest impact on results. CONCLUSIONS: Overall, PHiD-CV is expected to have better quality of life impact than PCV-13. Under price parity assumptions, PHiD-CV dominates PCV-13 because it also has a larger cost offsets.