This study aims to identify the relationships between Individualized Education Program (IEP) status and substance use. More than 122,000 eighth-, ninth-, and eleventh-grade students provided survey data in 2013. Analyses tested associations between IEP status and tobacco, alcohol, and marijuana use, accounting for emotional distress and demographic covariates. Approximately 10% of participants reported having an IEP; students with IEPs were significantly more likely to use substances than students without IEPs. In adjusted models, odds of cigarette smoking remained significantly elevated among students with IEPs. Education professionals may need to provide tailored substance use prevention programs to students with IEPs.