Objective: To examine the association between exposure to movie smoking and smoking initiation in a nationally representative sample of young U.S. adolescents. Design/Methods: We conducted a random digit-dial telephone survey of 6522 U.S. adolescents aged 10–14 years between June and October 2003. Using previously validated methods, we estimated exposure to movie smoking from 532 box-office hits released during the 5.5 years preceding the survey. The outcome was determined by asking the subjects whether or not they had ever tried smoking. Results: The distribution of age, sex, household income and census region in the unweighted sample were almost identical to U.S. Census 2000 estimates, indicating a highly representative sample. The population prevalence of smoking initiation was 0.103 (an estimated 2.2 million U.S. adolescents). Adolescents were grouped by quartile of movie smoking exposure. Smoking prevalence was 0.023 for adolescents in quartile 1, 0.063 for quartile 2, 0.112 for quartile 3, and 0.218 for quartile 4 (p < 0.001), and the association did not differ significantly by race or region of the country. The multivariate analysis controlled for sociodemographics, friend/sibling/family smoking, school performance, sensation seeking, rebelliousness, self esteem, and parenting style. Compared with quartile 1, the adjusted odds for trying smoking was 1.7 (95% confidence interval 1.1, 2.7) for quartile 2, 1.8 (1.2, 2.9) quartile 3, and 2.6 (1.7, 4.1) for quartile 4. The covariate adjusted attributable fraction was 0.38 (0.20, 0.56), suggesting that exposure to movie smoking is the primary independent risk factor for smoking initiation in 836 000 (421 000, 1 215 000) U.S. adolescents in this age group. Conclusions: This study implicates exposure to smoking in movies as a major risk factor for smoking initiation among U.S. adolescents, confirming previous work in smaller, regional samples.