•E-cigarette users had greater odds of nonmedical prescription drug use one year later.•E-cigarette users had greater risk of incidence of other drug use one year later.•In unadjusted prospective analyses, e-cigarette users had greater risk of alcohol use. As e-cigarette use continues to increase in the U.S., research is needed to understand its prospective risk for cigarette smoking and other substance use in young adulthood, including alcohol, marijuana, and nonmedical prescription drugs (NMPDs). This study used data from the Monitoring the Future (MTF) study a nationally representative annual survey of 12th graders (modal age 18) in the US. The analytic sample included 2014–2016 MTF cohorts that were selected and completed follow up one year later (modal age 19; n = 717). Using logistic regression, we examined cross-sectional and prospective associations of past 30-day e-cigarette use with past 30-day cigarette, alcohol, marijuana, and NMPD use. We examined prospective associations among the full sample and associations with incidence of each of these substances among those who reported no history of use in 12th grade. In cross-sectional analysis, those who reported past 30-day e-cigarette use at age 18 were more likely to report past 30-day cigarette use, alcohol use, marijuana use, and NMPD use at age 19. In multivariable longitudinal analysis, past 30-day e-cigarette users at age 18 were more likely to report past 30-day cigarette, marijuana, and NMPD use at age 19, including e-cigarette users who had no history of using these substances at age 18. This study suggests that e-cigarette use may be an indicator of future substance use risk in young adulthood. Adolescent e-cigarette users may benefit from secondary prevention efforts to mitigate this risk.