In the present study, middle schools were randomly assigned to receive the Life Skills Training program or to serve as a “treatment-as-usual” control group. All students (n = 2,042) completed pre-test, post-test, and long-term follow-up surveys. Analysis revealed that compared to students assigned to the control group, those who received LST showed significantly less overall lifetime illicit drug use, as well as lifetime marijuana use, marijuana intoxication, and lifetime non-medical pill use 13 years after they originally received the program. This study provides evidence that not only does the Life Skills Training program have immediate effects on substance use, but that the effects are long-term and durable.