Only a few studies have provided information on awareness, use, and harm perceptions of e-cigarettes in Europe. We fill the knowledge gap in Italy. We used data from a face-to-face survey conducted in 2013 of a sample of 3,000 individuals, representative of the Italian population aged ≥15 years (51.1 million inhabitants). Awareness of e-cigarettes was 91.1%; it was lowest among women (87.8%), the elderly (78.4%), those with less education (84.1%), and never-smokers (89.0%). Ever e-cigarette use was 6.8% overall and was inversely related to age, whereas no significant difference was observed according to sex. With regard to smoking status, 2.6% of never-smokers, 7.0% of ex-smokers, and 20.4% of current smokers tried the e-cigarette at least once. Regular e-cigarette use was 1.2% overall, 1.5% among men, and 0.9% among women, and it was highest among young (2.4%) and current smokers (3.7%). Among 36 e-cigarette regular users, 22.0% did not change their smoking habit, 67.7% reduced traditional cigarette consumption, and 10.4% quit smoking. After fewer than 3 years from the opening of the first Italian e-cigarette shop, more than 45 million Italians have heard about e-cigarettes, 3.5 million have tried e-cigaretts, and more than 600,000 Italians regularly use e-cigarettes. Three out of 4 e-cigarette users reported to have favorably modified their smoking habit; however, 90% of users did not quit smoking as a consequence of starting vaping e-cigarettes. Almost 900,000 Italian never-smokers, particularly young never-smokers, have tried this new and potentially addictive product at least once.