Background: States and national organizations spend millions annually on antismoking campaigns aimed at Youth. Much of the evidence for their effectiveness is based on cross-sectional studies. This study was designed to evaluate the effectiveness of a prominent national youth smoking-prevention campaign in the U.S. known as truth (R) that was launched in February 2000. Methods: A nationally representative cohort of 8904 adolescents aged 12-17 years who were interviewed annually from 1997 to 2004 was analyzed in 2008. A quasi-experimental design was used to relate changes in smoking initiation to variable levels of exposure to antismoking messages over time and across 210 media markets in the U.S. A discrete-time hazard model was used to quantify the influence of media market delivery of TV commercials on smoking initiation, controlling for confounding influences. Based oil the :.-esults of the hazard model, the number of youth nationally who were prevented front smoking from 2000 through 2004 was estimated. Results: Exposure to the truth campaign is associated with a decreased risk of smoking initiation (relative risk=0.80, p=0.001). Through 2004, approximately 450,000 adolescents were prevented from trying smoking nationwide. Factors negatively associated with initiation include African-American race (relative risk=0.44, p<0.001), Hispanic ethnicity (relative risk=0.74., p<0.001), completing high school (relative risk:=0.69, p<0.001), and living with both parents at baseline (OR=0.79, p<0.001). Conclusions: The current study strengthens the available evidence for antismoking campaigns as a viable strategy for preventing youth smoking. (Am J Prev Med 2009;36(5):379-384) (c) 2009 American Journal of Preventive Medicine