OBJECTIVES Pneumococcal vaccination schedules vary from 3 doses (2+1) to 4 doses (3+1) across Canadian provinces. We evaluate the effect of the variation in dosing strategy on health outcomes, costs, and cost-effectiveness of vaccination with the new 10-valent pneumococcal non-typeable Haemophilus influenzae protein-D conjugate vaccine (PHiD-CV) compared with the 7-valent pneumococcal conjugate vaccine (PCV-7). METHODS We developed an age-compartmental, population-based model to simulate the vaccine effect at steady-state for one year across the whole population. Model outputs include clinical endpoints and economic measures. Incremental Cost-Effectiveness Ratios (ICERs) are computed from the healthcare system perspective, calculating the incremental cost for incremental health gain. Productivity loss is reported separately and not included in the ICER. One-way and probabilistic sensitivity analyses were performed to evaluate the robustness of the model to variations in the underlying parameter assumptions. RESULTS Vaccination with 4 doses of PHiD-CV or PCV-7 would prevent an additional 296 and 222 cases of invasive pneumococcal disease (IPD) respectively compared with 3 doses. PHiD-CV (2+1) would prevent 116,493 more cases of Acute Otitis Media (AOM) than PCV-7 (2+1), and 94,076 more cases of AOM than PCV-7 (3+1). Furthermore, PHiD-CV (3+1) would prevent 76,875 more cases of AOM than PHiD-CV (2+1). The incremental cost-effectiveness analysis indicates that compared with no vaccination, PHiD-CV (2+1) is cost-effective. Compared with PHiD-CV (2+1), PHiD-CV (3+1) is cost-effective. However, PHiD-CV (less costly and higher health gain) dominates PCV-7. CONCLUSIONS Vaccination with 4 doses of PHiD-CV or PCV-7 offers a higher protection against IPD compared with 3 doses. PHiD-CV (2+1) prevents more cases of AOM compared with both PCV-7 (2+1) and PCV-7 (3+1). PHiD-CV (3+1) offers better protection against IPD and AOM compared with a 2+1 schedule. At price parity vaccination with PHiD-CV is the dominant strategy. From the societal perspective, PHiD-CV (3+1) dominates PHiD-CV (2+1).