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Importance To date, limited information is available on the characteristics of adolescents with e-cigarette, or vaping, product use–associated lung injury (EVALI). Objective To inform public health and clinical practice by describing differences in demographics, substance use behaviors, and clinical characteristics of EVALI among adolescents compared with adults. Design, Setting, and Participants Surveillance data reported to the Centers for Disease Control and Prevention during the 2019 EVALI outbreak were used to calculate adjusted prevalence ratios (aPRs) with 95% CIs and to test differences between 360 hospitalized or deceased adolescents vs 859 young adults and 936 adults with EVALI (N = 2155). Main Outcomes and Measures Demographics, substance use behaviors, and clinical characteristics. Results Included in this cross-sectional study were 360 hospitalized or deceased adolescents (age range, 13-17 years; 67.9% male) vs 859 young adults (age range, 18-24 years; 72.4% male) and 936 adults (age range, 25-49 years; 65.6% male) with EVALI. Adolescents diagnosed as having EVALI reported using any nicotine-containing (62.4%), any tetrahydrocannabinol (THC)-containing (81.7%), and both (50.8%) types of e-cigarette or vaping products. Informal sources for obtaining nicotine-containing and THC-containing e-cigarette or vaping products were more commonly reported by adolescents (50.5% for nicotine and 96.5% for THC) than young adults (19.8% for nicotine [aPR, 2.49; 95% CI, 1.78-3.46] and 86.9% for THC [aPR, 1.11; 95% CI, 1.05-1.18]) or adults (24.3% for nicotine [aPR, 2.06; 95% CI, 1.49-2.84] and 75.1% for THC [aPR, 1.29; 95% CI, 1.19-1.40]). Mental, emotional, or behavioral disorders were commonly reported; a history of attention-deficit/hyperactivity disorder was almost 4 times more likely among adolescents (18.1%) than adults (4.9%) (aPR, 3.74; 95% CI, 1.92-7.26). A history of asthma was more likely to be reported among adolescents (43.6%) than adults (28.3%) (aPR, 1.53; 95% CI, 1.14-2.05). Gastrointestinal and constitutional symptoms were more common in adolescents (90.9% and 97.3%, respectively) than adults (75.3% and 94.5%, respectively) (aPR, 1.20; 95% CI, 1.13-1.28 and aPR, 1.03; 95% CI, 1.00-1.06, respectively). Because of missing data, percentages may not be able to be calculated from data provided. Conclusions and Relevance Public health and clinical professionals should continue to provide information to adolescents about the association between EVALI and THC-containing e-cigarette or vaping product use, especially those products obtained through informal sources, and that the use of any e-cigarette or vaping product is unsafe. Compared with adults, it appears that adolescents with EVALI more frequently have a history of asthma and mental, emotional, or behavioral disorders, such as attention-deficit/hyperactivity disorder, and report nonspecific problems, including gastrointestinal and constitutional symptoms; therefore, obtaining a confidential substance use history that includes e-cigarette or vaping product use is recommended.