The number needed to vaccinate (NNV) is a metric commonly used to evaluate the public health impact of a vaccine as it represents the number of individuals that must be vaccinated to prevent one case of disease. Traditional calculations may underestimate vaccine benefits by neglecting indirect effects and duration of protection (DOP), resulting in NNV overestimation. This study evaluated the NNV for the pediatric 20-valent pneumococcal conjugate (PCV20) US immunization program, as compared to PCV13, with a unique approach to NNV. A multi-cohort, population-based Markov model accounting for indirect effects was employed to calculate the NNV of PCV20 to avert a case of pneumococcal disease, invasive pneumococcal disease (IPD), hospitalized non-bacteremic pneumonia (NBP), ambulatory NBP, and otitis media (OM), as well as to prevent antibiotic-resistant cases and antibiotic prescriptions. The mean NNV over a 25-year time horizon to prevent one case of pneumococcal disease was 6, with NNVs of 854 for IPD, 106 for hospitalized NBP, 25 for outpatient NBP, and 9 for OM, 11 for a course of antibiotic, and 4 for resistant disease. The mean NNV per year decreased over time, reflecting the DOP and increasing indirect effects over time. This study presents a novel approach to NNVs and shows that relatively few vaccinations are required to prevent disease. The decrease in NNV over time highlights the necessity of including DOP and indirect effects in NNV calculations, ensuring a more realistic assessment of a vaccine's impact.