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Background This study aims to examine the effects of comprehensive school-based tobacco control programs universally provided in schools of Seoul City, Korea. Methods To investigate the current status of school-based tobacco control programs, data were acquired from The Seoul Metropolitan Office of Education. To assess the capacity to implement tobacco control programs, the “Five-P's” matrix was used. The matrix consists of 5 domains: Policies, Program, People, Provision of funds, and Partnerships. To measure smoking behavior changes, we analyzed data from the 2015-2016 Korea Youth Risk Behavior Web-based Survey of adolescents (aged 12-18 years) in Seoul. Measures included smoking prevalence, age at smoking initiation, and proportion of quit attempts. Results Since 1999, Korean government has promoted school-based tobacco control programs. Less than 10% of schools had offered the programs until 2014. With the increase of tobacco tax in 2015, 100% schools started to provide comprehensive tobacco control programs including tobacco-free policies, anti-tobacco education and activities. Each school designated at least one teacher in charge. In 2016, a total of 3.9 million USD was invested in Seoul, with more than 70% of the funds allocated to a total of 1,300 schools, covering 976,000 students. Partnerships to enforce programs were also developed with community health centers. The prevalence of smoking among adolescents in Seoul was 7.0% in 2015 and 5.8% in 2016, a 17% reduction in one year. Smoking initiation age increased slightly from 12.7 to 12.9 years. Proportion of quit attempts continued to be as high as 73.5% in 2015 and 2016. Conclusions Universal coverage of school-based tobacco control programs appears to result in a significant reduction of youth smoking. Previously decreasing trend of smoking prevalence in Seoul adolescents has accelerated with the expansion of school-based tobacco control programs. The effectiveness of the programs needs to be monitored and continuously enhanced to achieve a tobacco-free generation.