Background: Dropping out of high school can have many negative socioeconomic and health outcomes. Prevention efforts targeted to youths and to those at risk of dropping out of high school might improve youths' the educational, employment and financial, and health outcomes. Method: Combined 2002 to 2014 National Surveys on Drug Use and Health was used to examine 12th grade aged youths by comparing past month (current) substance use between 12th grade students and 12th grade aged dropouts. Past month substance use examined in this report includes cigarette use, alcohol use, binge alcohol use, any illicit drug use, marijuana use, and nonmedical use of prescription type drugs. Results: Twelfth grade aged dropouts were more likely than 12th grade aged students to engage in current cigarette use, alcohol use, binge alcohol use, marijuana use, nonmedical use of prescription-type drugs, and use of any illicit drugs. Male 12th grade aged dropouts, female 12th grade aged dropouts, White 12th grade aged dropouts, and Black 12th grade aged dropouts were more likely than their peers who were 12th grade aged students to engage in substance use; however, Hispanic 12th grade aged dropouts and those still in school had similar percentages of past month use for all substances except cigarettes and binge alcohol use. Conclusion: Highlighting the prevalence of youth substance use for students who do not graduate high school may help policymakers continue to combat youth substance use, including efforts to raise awareness about the consequences of youth substance use and to improve prevention efforts.