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ABSTRACTUsing a test-negative case–control design, we aim to estimate influenza vaccine effectiveness (VE) against medically attended laboratory-confirmed influenza in Portugal in 2022/2023 season. Between week 41/2022 and week 14/2023, data on 592 patients with influenza-like illness aged 18 or more years old were collected by the national sentinel influenza surveillance system in primary care settings. Of those, 218 were positive for influenza and 374 were negative controls. We estimated seasonal influenza VE as (1-odds ratio)*100% of being vaccinated in laboratory-confirmed influenza cases vs. negative controls using logistic regression model adjusted for age group, sex, presence of chronic conditions, and month of symptoms onset. The seasonal VE was 59.3% (95% confidence interval (CI): 27.3 to 77.3) against any laboratory-confirmed influenza and not statistically significant 44.5% (95% CI: −5.6 to 70.8) against influenza A (H3N2). In the 2022/2023 season, characterized by early and low influenza activity and predominant A (H3N2) circulation, vaccination provided a moderate protection against medically attended laboratory-confirmed influenza in primary care.