e-Cigarette use and vaping marijuana (cannabis) are popular among US adolescents. Cannabidiol (CBD) is a compound found in the cannabis plant that has recently increased in use. To examine the prevalence of and factors associated with youths vaping CBD. This cross-sectional study included a nationally representative sample of students from middle and high schools (typical age, 11-18 years) in the US from the 2022 National Youth Tobacco Survey, conducted from January to May 2022. Demographic characteristics, harm perception of tobacco use, and vaping behaviors. The main outcomes were weighted prevalence and population estimates of ever and current (past 30-day) vaping of CBD overall and by e-cigarette use status. Multivariable logistic regression analyses were conducted to estimate the association of currently vaping CBD with demographic factors and e-cigarette and tobacco use behaviors stratified by current e-cigarette use status. The study included 28 291 participants (51.1% male; mean [SD] age, 14.5 [2.0] years). Among 2448 current e-cigarette users, 21.3% (95% CI, 18.4%-24.1%) reported any past-month vaping of CBD and 6.3% (95% CI, 4.7%-7.8%) reported that they did not know whether they had vaped CBD. Hispanic e-cigarette users were more likely than their non-Hispanic White peers to report currently vaping CBD (adjusted odds ratio [AOR], 1.9; 95% CI, 1.3-2.8). Current e-cigarette users with higher frequency (≥20 days vs ≤5 days) and longer duration (2-3 years or >3 years vs <1 year) of use were more likely to report currently vaping CBD (frequency: AOR, 1.5 [95% CI, 1.1-1.9]; 2-3 years: AOR, 2.2 [95% CI, 1.2-3.9]; 3 years: AOR, 3.2 [95% CI, 1.7-6.1]). Among 25 091 noncurrent e-cigarette users, 1.2% (95% CI, 1.0%-1.5%) reported currently vaping CBD and 2.3% (95% CI, 2.1%-2.6%) reported that they did not know. High school students (vs middle school students; AOR, 4.2; 95% CI, 2.8-6.1) and gay or lesbian (AOR, 2.9; 95% CI, 1.6-5.4) or bisexual (AOR, 2.7; 95% CI, 1.8-4.0) (vs heterosexual) youths were more likely to report vaping CBD, while those who perceived tobacco as dangerous (vs not dangerous; AOR, 0.4; 95% CI, 0.3-0.6) had lower odds of reporting vaping CBD. In this cross-sectional study of US middle and high school students, the prevalence of youths vaping CBD was high, particularly among e-cigarette users and Hispanic and sexual minority populations. The findings suggest that evidence-based educational campaigns, interventions, and public policy changes are needed to reduce the harmful health outcomes possible with vaping CBD among developing youths.