not-yet-known not-yet-known not-yet-known unknown We estimated XBB.1.5 vaccine effectiveness (VE) against symptomatic SARS-CoV-2 infection among adults aged ≥65 years during the 2023/24 JN.1 lineage-predominant period in a European multi-country test-negative case-control study at primary care level. We estimated VE adjusted by study site, age, sex, chronic conditions and onset date. We included 220 cases and 1733 controls. The VE was 48% (95% CI: 12–71), 23% (95% CI: -11–48) and 5% (95% CI: -92–56) among those with symptom onset 1–5 , 6–11, and ≥12 weeks after vaccination, respectively. XBB.1.5 vaccine provided short and moderate protection against JN.1 symptomatic infection.