Objectives: High-dose quadrivalent influenza vaccine (HD-QIV) was introduced during the 2021/22 influenza season in France for adults aged ≥65 years as an alternative to standard-dose quadrivalent influenza vaccines (SD-QIV). The aim of this study is to estimate the relative vaccine effectiveness (rVE) of HD-QIV versus SD-QIV against influenza-related hospitalisations in France. Methods: Community-dwelling individuals aged ≥65 years with reimbursed influenza vaccine claims during the 2021/22 influenza season were included from the French national health insurance database. Individuals were followed up from vaccination day to 30 June 2022, nursing home admission or death date. Baseline socio-demographic and health characteristics were identified from medical records over the five previous years. Hospitalisations due to influenza and other causes were recorded from 14 days after vaccination to end of follow-up. HD-QIV and SD-QIV vaccinees were matched using 1:4 propensity score matching with an exact constraint on age group, sex, week of vaccination and region. Incidence rate ratios (IRR) were estimated using zero-inflated Poisson or zero-inflated negative binomial regression models. Results: We matched 405,385 HD-QIV to 1,621,540 SD-QIV vaccinees. HD-QIV was associated with a 23.3% (95%CI: 8.4-35.8) lower rate of influenza hospitalisations compared with SD-QIV (69.5/100,000 person-years (PY) vs 90.5/100,000 py). Post-matching, we observed higher rates in the HD-QIV group for hospitalisations non-specific to influenza and for negative control outcomes, suggesting residual confounding by indication. Conclusions: HD-QIV was associated with lower influenza-related hospitalisation rates versus SD-QIV, consistent with existing evidence, in the context of high SARS-CoV-2 circulation in France and likely prioritisation of HD-QIV for older/more comorbid individuals.