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Background: To reduce smoking uptake in adolescents, the medical students' network Education Against Tobacco (EAT) has developed a school-based intervention involving a face-aging mobile app (Smokerface)., Methods: A two-arm cluster-randomized controlled trial was conducted, evaluating the 2016 EAT intervention, which employed the mobile app Smokerface and which was delivered by medical students. Schools were randomized to intervention or control group. Surveys were conducted at baseline (pre-intervention) and at 9, 16, and 24 months post-intervention via paper & pencil questionnaires. The primary outcome was the difference in within-group changes in smoking prevalence between intervention and control group at 24 months., Results: Overall, 144 German secondary schools comprising 11,286 pupils participated in the baseline survey, of which 100 schools participated in the baseline and at least one of the follow-up surveys, yielding 7437 pupils in the analysis sample. After 24 months, smoking prevalence was numerically lower in the intervention group compared to control group (12.9 % vs. 14.3 %); however, between-group differences in change in smoking prevalence between baseline and 24-months follow-up (OR=0.83, 95 %-CI: 0.64-1.09) were not statistically significant (p = 0.176). Intention to start smoking among baseline non-smokers declined non-significantly in the intervention group (p = 0.064), and remained essentially unchanged in the control group, but between-group differences in changes at the 24-months follow-up (OR=0.88, 0.64-1.21) were not statistically significant (p = 0.417)., Conclusion: While a trend towards beneficial effects of the intervention regarding smoking prevalence as well as intention to start smoking among baseline non-smokers was observed, our smoking prevention trial demonstrated no significant effect of the intervention., Competing Interests: Declaration of Competing Interest TJB programmed the Smokerface App and is therefore formally the owner/rights holder. In 2017, he was offered and accepted 500 Euro per year from another German tobacco prevention charity (ginko Stiftung für Prävention, Germany) to license the Smokerface App for their school-based prevention efforts,with no influence to this study. TJB is also the owner of Smart Health Heidelberg GmbH, a software company which develops digital utehealth apps. Werner Seeger received consulting fees from United Therapeutics, Tiakis Biotech AG, Liquidia, Pieris Pharmaceuticals, Abivax, Pfizer, Medspray BV, outside the submitted work. The other authors declare no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)