When influenza vaccination is ineffective in preventing influenza virus infection, it may still reduce the severity of influenza-associated disease. Here, we estimate the effect of influenza vaccination in preventing severe outcomes e.g. intensive care unit (ICU) admission and death, even though it did not prevent influenza virus infection and subsequent hospitalisation. Methods: An observational case-case epidemiological study was carried out in 12 sentinel hospitals in Catalonia (Spain) over six influenza seasons 2010/11-2015/16. Cases were individuals with severe laboratory-confirmed influenza virus infection and aged 18 years and older. For each reported case we collected demographic, virological and clinical characteristics. Logistic regression was used to estimate the crude, adjusted odd ratios (aOR) and 95% confidence intervals (CI). Results: Of 1,727 hospitalised patients included in the study, 799 were female (46.7%), 591 (34.2%) were admitted to the ICU and 223 (12.9%) died. Influenza vaccination uptake was lower in cases that required ICU admission or died (21.2% vs 29.7%, p < 0.001). The adjusted influenza vaccination effectiveness in preventing ICU admission or death was 23% (95% CI: 1 to 40). In an analysis restricted to sex, age group and antiviral treatment, influenza vaccination had a positive effect on disease severity in all age groups and categories. Conclusions: We found that influenza vaccination reduced the severity of disease even in cases where it did not prevent infection and influenza-associated hospitalisation. Therefore, increased vaccination uptake may reduce complications, ICU admission and death.