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Influenza vaccination may be effective in preventing influenza infection and may reduce the risk of influenza-associated pneumonia. The study aim was to evaluate the effect of influenza vaccination in preventing pneumonia when it failed to prevent influenza hospitalization. This was a case–control study comparing hospitalized cases of influenza with and without pneumonia in patients aged ≥18 years in 16 hospitals in Catalonia over 10 influenza seasons (2010–11 to 2019–20). Data on sociodemographic, virological characteristics, comorbidities, vaccination history, and antiviral treatment were collected and analysed. The crude odds ratio (OR) and adjusted OR (aOR) with the corresponding 95% confidence interval (CI) values were calculated. In total, 5080 patients hospitalized for severe influenza were included, 63.5% (3224/5080) of whom had pneumonia—mostly men (56.8%; 1830/3224) and mostly in the ≥75 age group (39.3%; 1267/3224)—and of whom 14.0% died (451/3224). Virus A and virus B accounted for 78.1% (2518/3224) and 21.9% (705/3224) of influenza types, respectively. Starting antiviral treatment ≤48 h after symptom onset (aOR = 0.69; 95%CI: 0.53–0.90) and a history of seasonal influenza vaccination (aOR = 0.85; 95%CI: 0.72–0.98) were protective factors in developing pneumonia. Adherence to seasonal influenza vaccination and starting antiviral treatment within 48 h of symptom onset can reduce pneumonia risk in severe influenza cases.