The outbreak of the pandemic influenza H1N1 2009 (swine flu) between March and April 2009 challenged the health services around the world. Indeed, misconceptions and worries have led the public to refuse to comply with precautionary measures. Moreover, there have been limited efforts to develop models incorporating cognitive, social-contextual, and affective factors as predictors of compliance with recommended behaviors. The aim of this study was to apply a social-cognitive model of risk perception and individual response to pandemic influenza H1N1 in a representative sample of Italian population. A sample of 1,010 Italians of at least 18 years of age took part in a telephone survey. The survey included measures of perceived preparedness of institutions, family members and friends’ levels of worry, exposure to media campaigns (social-contextual factors), perceived coping efficacy, likelihood of infection, perceived seriousness, personal impact, and severity of illness (cognitive evaluations), affective response and compliance with recommended behaviors. Results demonstrated that affective response fully mediated the relationship between cognitive evaluations and social-contextual factors (with the exception of exposure to media campaigns) and compliance with recommended behaviors. Perceived coping efficacy and preparedness of institutions were not related to compliance with recommended behaviors.