BACKGROUND: To better establish the value of vaccination against influenza viruses, we estimated vaccine-averted influenza illnesses among young children and older adults in Chile, Guyana, and Paraguay. METHODS: We gathered country- and target population-specific data on monthly influenza hospitalizations, vaccine coverage, and vaccine effectiveness from surveillance records and immunization registries during 2013-2018. We applied a static compartmental model to estimate differences in the number influenza-associated respiratory disease events (symptomatic nonhospitalized illnesses, medically attended illnesses, hospitalizations) in the presence and absence of influenza vaccination programs. RESULTS: Between 2013 and 2018, vaccinating 68% of children aged 6-23 months in Chile averted an annual mean of 14 617 nonhospitalized, 9426 medically attended, and 328 hospitalized influenza illnesses
vaccinating 28% of children aged 6-23 months in Paraguay averted 1115 nonhospitalized, 719 medically attended, and 25 hospitalized influenza illnesses. Vaccinating 59% of older adults in Chile averted an annual mean of 83 429 nonhospitalized, 37 079 medically attended, and 1390 hospitalized influenza illnesses
vaccinating 36% of older adults in Paraguay averted an annual mean of 3932 nonhospitalized, 1748 medically attended, and 66 hospitalized influenza illnesses. In Guyana, a hypothetical campaign vaccinating 30% of children aged <
5 years could have prevented an annual 1496 nonhospitalized, 971 medically attended, and 10 hospitalized influenza illnesses. Vaccinating 30% of adults aged ≥65 years could have prevented 568 nonhospitalized, 257 medically attended, and 10 hospitalized influenza illnesses. CONCLUSIONS: Influenza vaccination averted tens of thousands of illnesses and thousands of hospitalizations in Chile and Paraguay
influenza vaccination could have had a proportional benefit in Guyana.