Background: Illicit drug use by school-aged teens can adversely affect their health and academic achievement. This study used a survey administered in schools to assess the prevalence of problematic drug use among teenagers in a Midwestern community. Methods: Self-report data were collected from 11th- and 12th-grade students (N = 3974) in 16 school districts in the Dayton, Ohio, area. Students responded to a drug use survey that also included CRAFFT, a brief substance abuse screening instrument. Binomial and zero-inflated Poisson regressions were used to examine the association between CRAFFT scores and drug use practices, including abstinence. Results: More than one third of students had CRAFFT scores suggestive of problematic use. Of these, 14.1% had scores suggesting drug dependence. Although alcohol, marijuana, and tobacco were the drugs most commonly used, an array of other drugs including opioids, benzodiazepines, stimulants, hallucinogens, and dextromethorphan were also commonly used. Higher CRAFFT scores were associated with a greater number of drugs used (p less than 0.0001). Proportionately more 12th graders than 11th graders had CRAFFT scores indicating problems (p less than 0.0001). Among 12th graders, boys were more likely than girls to have CRAFFT scores indicating dependence (p = 0.01). Conclusions: The results suggest that problematic drug use among high school students is more prevalent than has been recognized previously. CRAFFT can be used easily to assess the prevalence of problematic drug use among teenagers in school settings. CRAFFT results can also inform prevention and intervention activities, particularly if the CRAFFT instrument is paired with a drug use survey. (Contains 3 tables and 1 figure.)