PurposeThe purpose of the study was to identify proximal links between electronic cigarette (e-cigarette) use and numerous indicators of adjustment, delinquency, and other substance use in adolescence, beyond prior levels and confounders. MethodsThe ongoing Millennium Cohort Study is a nationally representative, intergenerational, longitudinal study of children born 2000–2001 in the United Kingdom followed from birth to age 14 years (n = 11,564 adolescents and their parents). A series of ordinary least squares and logistic regressions compared 14-year-old e-cigarette only users to never users and to combustible/dual users on 10 measures of adjustment (school engagement, well-being, and self-esteem), delinquency (theft, vandalism, disorderly conduct, and graffitiing), and other substance use (frequent alcohol use, heavy drinking, and marijuana use). Controls included each outcome variable measured at age 11 years and prospectively assessed parent and child confounders (e.g., parent education, child externalizing and internalizing behaviors, cognitive test scores, gender, and race/ethnicity). ResultsAt age 14 years, e-cigarette only users (approximately 7% of youth) had a higher risk of adolescent adjustment problems, delinquent behavior, and substance use relative to nonusers (75% of youth), but lower risk relative to combustible cigarette/dual users (18% of youth), even after controlling for a host of childhood confounders. ConclusionsPositive links shown here between e-cigarette use and poor adjustment, delinquency, and other substance use in adolescence, coupled with accumulating evidence that e-cigarettes substantially increase youths’ likelihood of combustible smoking, indicate that e-cigarettes are part of an emerging pattern of health-risk behaviors and poor adjustment for some youth.