<p>Respiratory syncytial virus (RSV) causes a substantial health burden among infants and older adults. Prefusion F protein-based vaccines have shown high efficacy against RSV disease in clinical trials, offering promise for mitigating this burden through maternal and older adult immunization. Employing an individual-based model, we evaluated the impact of RSV vaccination on hospitalizations and deaths in 13 high-income countries, assuming that the vaccine does not prevent infection or transmission. Using country-specific vaccine uptake rates for seasonal influenza, we found that vaccination of older adults would prevent hospitalizations by a median of 35–64% across the countries studied here. Vaccination of pregnant women could avert infant hospitalizations by 5–50%. Reductions in RSV-related mortality mirrored those estimated for hospitalizations. While substantial hospitalization costs could be averted, the impact of vaccination depends critically on uptake rates. Enhancing uptake and accessibility is crucial for maximizing the real-world impact of vaccination on reducing RSV burden among vulnerable populations.</p>