OBJECTIVES: To estimate the clinical and economic impact of vaccinating a birth cohort with the newly licensed 10-valent pneumococcal non-typeable haemophilus influenzae protein-D conjugate vaccine (PHiD-CV) compared with the 13-valent pneumococcal candidate vaccine (PCV-13) over lifetime. METHODS:  We developed an age-compartmental, deterministic, and static Markov model to project the impact of pneumococcal vaccination on the incidence of pneumococcal infections from birth through lifetime in specific age–time units (months). The disease types modeled include invasive pneumococcal disease (IPD), community acquired pneumonia (CAP) and acute otitis media (AOM), assuming 11 health states per condition. Serotype distributions per disease type and age group were incorporated. Costs, health gains and cost-effectiveness were estimated. A 4-dose (3+1) schedule is assumed for both vaccines with 100% vaccine coverage. All analyses were performed from the Canadian health care system perspective assuming a price parity of $70 per dose. The model uses Canada specific epidemiological data. Both outcomes and cost were discounted at 3.5%. Various sensitivity analyses were performed to assess the impact of changes in the key assumptions of the model. RESULTS: Compared with PCV-13, vaccinating a birth cohort of 340,000 with PHiD-CV in Canada is expected to prevent 92,026 additional AOM myringotomies and 108,978 ambulatory visits due to AOM over lifetime. The impact of the two vaccines on IPD is projected to be comparable. At price parity of $70 per dose, the total savings to the Canadian health care system over the lifetime of the cohort is projected to be $58.7M for PHiD-CV compared to PCV-13. Sensitivity analyses indicate that AOM and bacteraemia have the biggest impact on the model. CONCLUSIONS: Overall, the clinical benefits of the two vaccines are comparable on IPD. QALYs are improved for PHiD-CV compared to PCV-13 because of the greater impact on AOM. PHiD-CV is projected to be cost-saving to the Canadian health care system compared to PCV-13.