INTRODUCTION E-cigarettes are popular among youth. There are concerns that e-cigarettes attract youth that would otherwise not use addictive substances. While e-cigarettes are thought to be less harmful than tobacco, there is reason for caution. We examined to what extent adolescent e-cigarette users have characteristics associated with increased risk of substance use.METHODS We collected cross-sectional survey data in 2018 among 10 schools throughout the Netherlands and Belgium (N=2794; age 10-18 years). We examined differences in characteristics and behaviors between e-cigarette ever users and never users, and former users and current users. We also explored differences in use of flavors and use of nicotine.RESULTS Compared to never-users, e-cigarettes users more often were boys, older, had lower education level, non-Dutch or non-Belgian ethnicity, reported more combustible tobacco use, more smoking family members or family with problematic substance use, more smoking friends, more depressive symptoms, more impulsivity, more delinquent behavior, were more susceptible to smoking, had more positive smoking expectancies, and more ever use of substances. Users of non-tobacco flavored e-cigarettes and e-cigarettes without nicotine had fewer characteristics known to be related to an increased risk of substance use, compared to users of tobacco-flavored e-cigarettes and e-cigarettes with nicotine.CONCLUSIONS Adolescent e-cigarette users are more like youths who experiment with addictive substances compared to non-users. Thus, e-cigarettes users were more likely to use substances, regardless of whether they used e-cigarettes first. This may not be true for all types of e-cigarettes, as users of e-cigarettes without nicotine or with non-tobacco flavors were less like youths who experiment with substances.