Background: The Gateway Drug Theory suggests that licit drugs, such as tobacco and alcohol, serve as a "gateway" toward the use of other, illicit drugs. However, there remains some discrepancy regarding which drug--alcohol, tobacco, or even marijuana--serves as the initial "gateway" drug subsequently leading to the use of illicit drugs such as cocaine and heroin. The purpose of this investigation was to determine which drug (alcohol, tobacco, or marijuana) was the actual "gateway" drug leading to additional substance use among a nationally representative sample of high school seniors. Methods: This investigation conducted a secondary analysis of the 2008 Monitoring the Future 12th-grade data. Initiation into alcohol, tobacco, and other drug use was analyzed using a Guttman scale. Coefficients of reliability and scalability were calculated to evaluate scale fit. Subsequent cross tabulations and chi-square test for independence were conducted to better understand the relationship between the identified gateway drug and other substances' use. Results: Results from the Guttman scale indicated that alcohol represented the "gateway" drug, leading to the use of tobacco, marijuana, and other illicit substances. Moreover, students who used alcohol exhibited a significantly greater likelihood of using both licit and illicit drugs. Conclusion: The findings from this investigation support that alcohol should receive primary attention in school-based substance abuse prevention programming, as the use of other substances could be impacted by delaying or preventing alcohol use. Therefore, it seems prudent for school and public health officials to focus prevention efforts, policies, and monies, on addressing adolescent alcohol use. (Contains 2 tables and 1 figure.)