Background
Vaccination is a primary preventive strategy to reduce influenza morbidity and mortality. Assessing how influenza vaccine effectiveness translates into real?world reductions in severe outcomes in vulnerable populations is essential for public health decision?making. This study aimed to estimate the impact of the influenza vaccination program in Portugal on influenza-related hospitalizations in?≥?65 years old population during the 2022/23-2024/25 seasons.

Methods
Using data on influenza surveillance, hospitalizations, vaccine coverage, and vaccine effectiveness, we estimated the number of averted events (NAE), the prevention fraction (PF), and the number needed to vaccinate to prevent one hospitalization (NVN) per season in the population aged ≥65 years. Monte Carlo simulations were used to estimate the 95% uncertainty intervals of all impact parameters.

Results
Influenza vaccine effectiveness varied across seasons from 32% to 45%, depending on the circulating strain. Vaccine coverage ranged from 66% to 73%. In 2022/23, with predominant A(H3N2) circulation, vaccination averted 68 (95%UI 31.5-107.0) hospitalizations per 100000 inhabitants, corresponding to PF of 23.4% (95%UI 12.4-32.4) and NNV of 974 (95%CI 682-2310). In 2023/24, with A(H1N1)pdm09 predominance, NAE was 69.8 (95%UI 38.8-102.1) hospitalizations per 100000, PF 23.7% (95%UI 14.8-21.3), and NNV 945 (95%UI 646-1700). In 2024/25, with co-circulation of A(H3N2) and B/Victoria, we observed a higher NAE of 95.7 (95%UI 50.9-140.4) per 100000, with PF of 31.5% (95%UI 19.7-40.3) and NNV of 731 (95%UI 498-1373).

Conclusions
The seasonal influenza vaccination provided consistent benefits in adults aged ≥65, preventing a significant number of hospitalizations even in seasons with moderate vaccine effectiveness. Our findings support public health communication aimed at increasing vaccination coverage in Portugal and mitigating the impact of influenza epidemics on population health and the healthcare system.