Abstract Introduction Adolescent vaping remains a problem in the United States, yet little is known about what health warning themes most discourage vaping among adolescents. We sought to identify the most compelling themes for vaping warnings for US adolescents. Methods Participants were a national probability sample of 623 US adolescents aged 13–17 years, recruited in the summer of 2020. Adolescents were randomized to one of the five warning message themes about the potential health effects of vaping: 1. chemical harms, 2. lung harms, 3. Coronavirus Disease 2019 (COVID-19) harms, 4. nicotine addiction, or 5. control (messages about vape litter). The primary outcome was perceived message effectiveness (PME; 3-item scale). Secondary outcomes were negative affect (fear), attention, anticipated social interactions, and message novelty. Results Adolescents rated the chemical, lung, and COVID-19 harms warning messages higher on PME than nicotine addiction and control (all p < .05), while nicotine addiction was rated higher than control (p < .05). The chemical, lung, and COVID-19 harms warning themes also elicited greater negative affect than nicotine addiction and control (all p < .05). For all other secondary outcomes, the COVID-19 harms warning message theme was rated higher than nicotine addiction and control (all p < .05). Conclusion Adolescents perceived warning message themes about lung, chemical and COVID-19 health effects of vaping as more effective than nicotine addiction. To discourage vaping, the FDA and others should communicate to youth about the health effects of vaping beyond nicotine addiction. Implications Adolescents rated warning message themes about the lung, chemical, and COVID-19 health effects of vaping as more effective than nicotine addiction, while nicotine addiction was rated as more effective than control themes about vaping litter. To discourage vaping among adolescents, health messaging should expand message themes to communicate about a broader set of health effects of vaping beyond nicotine addiction.