The purpose of this brief was to compare the prevalence of risky substance use behaviors (tobacco, alcohol, and illicit drug use) among adolescents 12 to 17 years of age residing in nonmetropolitan (rural) and metropolitan (urban) counties. Combined 2017-2018 data from the National Survey on Drug Use and Health (NSDUH) was used to compare the prevalence of risky substance use among rural and urban adolescents. Significant differences were found in tobacco use and some subcategories of illicit drugs, notably methamphetamine.