BackgroundThis study explores the association between psychosocial stressors and current e-cigarette use among adolescents in the United States.MethodsWe used data from 12,767 participants in the 2019 National Youth Risk Behavioral Survey to examine the association between psychosocial stressors (bullying, sexual assault, safety-related absence from school, depressive symptoms, suicidal ideation, physical altercation, and weapon threats) and past-30-day e-cigarette use using multivariable-adjusted logistic regression models. We examined the association for each stressor and then as a burden score (0–7). To compare the strength of the association between stressors and current e-cigarette use to current combustible cigarette use, we additionally examined the association between each stressor and current combustible cigarette use.ResultsApproximately 32.7% reported current e-cigarette use. The weighted prevalence of current e-cigarette use was higher among individuals who experienced stressors than those who did not. For example, bullying (43.9% vs. 29.0%). Similar prevalence patterns were seen among other stressors. Individuals who experienced stressors had significantly higher adjusted odds of current e-cigarette use than those who did not (OR [Odds Ratio] range: 1.47–1.75). Similarly, individuals with higher burden scores had a higher prevalence (zero [20.5%], one [32.8%], two [41.4%], three [49.6%], four to seven [60.9%]) and higher odds of current e-cigarette use (OR range: 1.43–2.73) than those with a score of zero. The strength of the association between the stressors and e-cigarette use was similar to that between the stressors and combustible cigarette use.ConclusionThe study demonstrates a significant association between psychosocial stressors and adolescent e-cigarette use, highlighting the potential importance of interventions, such as targeted school-based programs that address stressors and promote stress management, as possible means of reducing adolescent e-cigarette use. Future research directions include exploring underlying mechanisms linking stressors to e-cigarette use and evaluating the effectiveness of interventions addressing stressors in reducing adolescent e-cigarette use.Supplementary InformationThe online version contains supplementary material available at 10.1186/s12889-023-16031-w.