In the United States, approximately 900,000 youths smoke their first cigarette each year (1). Health communication interventions are evidence-based strategies for preventing the initiation of tobacco use, promoting and facilitating cessation, and changing beliefs and attitudes about tobacco use (2,3). This report describes the association between the Food and Drug Administration's (FDA's) first national tobacco public education campaign, The Real Cost, and rates of smoking initiation among youths in the United States from 2014 to 2016. A nationally representative cohort study of youths (N = 5,185) was conducted during November 2013-March 2016. Results from a discrete-time survival model indicate that, among youths who reported never having smoked a cigarette in the baseline survey, the odds of reporting smoking initiation at follow-up were lower among youths with frequent exposure to campaign advertisements than among those with little or no exposure (adjusted odds ratio [aOR] = 0.70, 95% confidence interval [CI] = 0.55-0.91). Based on the results of the model, The Real Cost is associated with an estimated 348,398 U.S. youths aged 11-18 years who did not initiate smoking during February 2014-March 2016. Sustained youth-focused tobacco education campaigns, such as The Real Cost, can help speed progress toward preventing tobacco use among youths in the United States.