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Objective Adolescents are exposed to a variety of tobacco products in Greece. On the other hand, tobacco industry promotional strategies aim to critically increase the attractiveness of their products so that adolescents start to use them. According to the literature, school-based preventive interventions may have positive effects in discouraging adolescents from initiating smoking. This study aims to present activities of a school-based program for smoking prevention in Greek adolescents. Methods The intervention was co-designed and implemented in one high school located in Attica, Greece, in the 2018-2019 school year among 10th grade adolescents. Results The educational process included the provision of information on the health effects of smoking and nicotine products, information on tobacco product ingredients, training of social skills to resist peer pressure, peer-led activities and discussions, group problem-solving and role-playing under different peer and social pressure situations. Conclusions The program was well received by the adolescents and covered key priority domains of a tobacco prevention curriculum. Within the context of this pilot study, we did not use a control group, and the effects of the intervention were not assessed. An appropriate evaluation of the program would give a better understanding of its potential effectiveness in reducing tobacco use within the public school system in Greece.