• 60% of youth reported exposure to e-cigarette advertisements through at least one channel. • E-cigarette advertisements had a long-term indirect impact on youth e-cigarette use. • There was no enduring direct influence of e-cigarette advertisements. • Adolescents with fewer internalizing problems were more vulnerable to advertising influence. • Adolescents with higher levels of internalizing problems perceived e-cigarettes as less harmful. Prior research indicates a direct, short-term effect of e-cigarette advertising on e-cigarette use among youth. This study seeks to investigate the long-term effects of e-cigarette advertisements and disparities in exposure among adolescents with different levels of internalizing problems. Panel data of the Population Assessment of Tobacco and Health (PATH) Study Waves 3–5 (2015–2019) were analyzed. Youth aged 12–17 who were non-e-cigarette users at the time of Wave 3 were included (n = 4,678). A moderated mediation model was employed to examine the mediating role of perceived harm of e-cigarettes and the moderating effect of internalizing problems. Exposure to e-cigarette advertisements in Wave 3 predicted lower harm perception of e-cigarette in Wave 4 (bp = -0.055, p <.01), leading to more e-cigarette use in Wave 5 (bp = -0.042, p <.001). While e-cigarette advertisements exhibited a lasting indirect effect (bp = 0.002, p <.05), there was no long-term direct effect (bp = 0.017, p >.05) on youth e-cigarette use. Furthermore, a moderating effect of internalizing problems was observed (bp = 0.107, p <.05). E-cigarette advertisements can exert a lasting influence indirectly by diminishing harm perception, particularly among those with lower internalizing problems. Adolescents with higher internalizing problems exhibit lower susceptibility to advertisement influence, yet their perceived harm of e-cigarettes is notably lower than their peers with fewer internalizing problems. These disparities underscore the need for tailored prevention strategies: implementing anti-e-cigarette education programs for adolescents with low internalizing problems and providing mental health care for those facing internalizing challenges. Regulatory measures targeting e-cigarette advertising are also crucial. [ABSTRACT FROM AUTHOR]