Through its effects on the immune system, smoking may facilitate influenza virus infection, its severity and its most frequent complications. The objective was to investigate the smoking history as a risk factor for influenza hospitalization and influenza vaccine effectiveness in elderly smokers/ex-smokers and non-smokers.

We carried out a multicenter case–control study in the 2013–2014 and 2014–2015 influenza seasons. Cases aged ≥65 years and age-, sex-matched controls were selected from 20 Spanish hospitals. We collected epidemiological variables, comorbidities, vaccination history and the smoking history. The risk of hospitalization due to smoking (current smokers and ex-smokers) was determined using the adjusted odds ratio (aOR) with conditional logistic regression models. Vaccine effectiveness (VE) was calculated using the formula: VE = (1 – aOR) × 100.

We studied 728 cases and 1826 controls. Cases had a higher frequency of smoking (47.4% vs 42.1%). Smoking was associated with an increased risk of influenza hospitalization (aOR = 1.32, 95% CI: 1.04–1.68). Influenza vaccine effectiveness in preventing hospitalization was 21% (95% CI: -2 to 39) in current/ex-smokers and 39% in non-smokers (95% CI: 22–52).

A history of smoking may increase the risk of hospitalization in smokers and ex-smokers. Preventing smoking could reduce hospitalizations due to influenza. Smokers and ex-smokers should be informed of the risk of hospitalization due to influenza infection, and encouraged to stop smoking. Smokers should be considered an at-risk group to be aggressively targeted for routine influenza vaccination.