Background: Annual estimates of seasonal influenza vaccine effectiveness can guide global risk communication and vaccination strategies to mitigate influenza-associated illness. We aimed to evaluate vaccine effectiveness in countries using the 2023 southern hemisphere influenza vaccine formulation.

Methods: We evaluated end-of-season influenza vaccine effectiveness across eight countries (Argentina, Australia, Brazil, Chile, New Zealand, Paraguay, Thailand, and Uruguay) that used the 2023 southern hemisphere vaccine formulation, with use of a test-negative design. All patients who attended participating hospitals with severe acute respiratory illness were tested by RT-PCR for influenza. We calculated country-specific, network-specific, and pooled vaccine effectiveness against hospitalisation. For countries with sufficient data, we also calculated vaccine effectiveness against intensive care unit (ICU) admission by comparing the odds of vaccination among test-positive cases to that among test-negative controls. We evaluated vaccine effectiveness for groups prioritised for vaccination (young children aged 1-4 years, people aged 5-64 years with underlying health conditions, and older adults aged ≥65 years).

Findings: From March 5 to Nov 27, 2023, 31 368 individuals were admitted to hospital with severe acute respiratory infection in the eight included countries. Of these, 12 609 individuals admitted to hospital (6452 [51·2%] female and 6157 [48·8%] male) who met inclusion criteria and had complete data were included in the analysis, including 4388 test-positive cases and 8221 test-negative controls. Pooled vaccine effectiveness against hospitalisation with any influenza virus was 51·9% (95% CI 37·2-66·7), with substantial heterogeneity across countries (I2 74%). Vaccine effectiveness against ICU admission from any influenza virus was 67·7% (44·5-81·2) in Chile and 69·7% (45·3-83·3) in Australia. Vaccine effectiveness estimates against hospitalisation were highest for young children (70·9% [47·5-94·4]) and lowest for older adults (47·7% [24·9-70·5]).

Interpretation: Across eight countries, 2023 southern hemisphere vaccines were effective in reducing hospitalisations from influenza illness. Use of common protocols can facilitate data pooling to provide a comprehensive evaluation of vaccine effectiveness across settings.