Background: E-cigarette prevention education aims to mitigate adolescent e-cigarette use. Such education is increasingly delivered through virtual/video-based teaching platforms (e.g. Zoom, Google Classrooms). However, there is little evidence about the effectiveness of virtual e-cigarette education compared to in-person education on adolescents' knowledge about e-cigarettes, perceived addictiveness and intent to try e-cigarettes, cigarettes, and marijuana. Objective: To evaluate the effectiveness of virtual e-cigarette education compared to in-person education on student knowledge and perceived addictiveness of e-cigarettes and intent to try e-cigarettes. Design, Setting and Method: We conducted a pre- and post-education evaluation among 10 middle and high school students in the Greater Birmingham area, Alabama, who were non-randomly assigned to receive either virtual (n = 745) or in-person e-cigarette education (n = 286) (mean age: 14.36 years). The study used a 25-minute educational presentation about the health effects of e-cigarettes, the risks of second- and third-hand smoke, the addictive nature of nicotine, and marketing strategies of e-cigarette companies. Participants completed a 10-minute self-administered survey immediately before and after the presentation. Results and conclusion: Except for certain e-cigarette knowledge-related items, our study shows that both virtual and in-person education had similar effects on improving knowledge about e-cigarettes, increasing perceived addictiveness and reducing intent to try e-cigarettes, cigarettes and marijuana among participants. Virtual education may be applied where in-person education is not feasible (e.g. in rural communities).