• Marijuana, alcohol and cigarettes are three gateway drugs for teens.
• Teen use of any one gateway drug is associated with use of the other two.
• Teen use of any one gateway drug is associated with use of illicit drugs.
• Improving teen health and reducing addiction can begin with reducing teen drug use.
• Prevention should focus on approaches that reduce use of all substances simultaneously.
The prevalence of substance use disorders in adults is higher if substance use is initiated during adolescence, underscoring the importance of youth substance use prevention. We examined whether the use of one substance by adolescents is associated with increased risk for using any other substance, regardless of use sequences. In 2017 we examined data from 17,000 youth aged 12–17 who participated in the 2014 National Survey on Drug Use and Health, a sample of nationally representative data on substance use among the U.S. civilian, noninstitutionalized population aged 12 or older. Descriptive analyses and multivariable logistic regression models were applied. After controlling for age, sex, and race/ethnicity, compared with youth without past-month marijuana use, youth with past-month marijuana use were 8.9 times more likely to report past-month cigarette use, 5.6, 7.9 and 15.8 times more likely to report past-month alcohol use, binge use, or heavy use (respectively), and 9.9 times more likely to report past-month use of other illicit drugs. The prevalence of past-month use of cigarettes, marijuana, and other illicit drugs was significantly higher among past-month alcohol users compared with youth without past-month alcohol use, and increased as intensity of alcohol use rose. Among past-month cigarette smokers, the prevalence of marijuana, other illicit drugs, and alcohol use were each significantly higher than youth without past-month cigarette use. Youth marijuana use, cigarette smoking, or alcohol consumptioni s associated with other substance use. This finding has importance for youth prevention, supporting a message no use by youth of any substance.