New-generation pneumococcal conjugate vaccines (PCVs) are available to replace PCV-13 for childhood and adult immunization. Besides cost-effectiveness evaluations which have highly variable results, the comparative immunogenicity of these new vaccines (PCV15, PCV20, PCV21) and their coverage of invasive pneumococcal disease (IPD) and carriage strains in different age-groups should be regarded as well as the antibody susceptibility, antibiotic resistance, invasiveness and virulence of serotypes included in each vaccine. Based on the Canadian experience, these topics are discussed. The optimal strategy would be a 2+1 PCV20 schedule for children, PCV21 for elderly adults and a dual PCV20+PCV21 schedule for adults at very high IPD risk. Shifting from PCV-13 to PCV-15 for children entails a risk of increased IPD incidence in adults because additional serotypes are of low virulence and could be replaced by more invasive and virulent serotypes. This risk can be reasonably excluded if PCV-20 replaces PCV-13 as the former covers additional serotypes being highly invasive and virulent. It is recognized that off-label use of PCV-20 according to a 2+1 schedule could be problematic for some jurisdictions as this is not authorized in all countries. In Canada, however, the 2+1 PCV20 schedule was authorized based on the same dataset submitted elsewhere.