The purpose of this article is to investigate polysubstance use among college student-athletes and determine whether use is independent of gender, race, season status, and athletic division. College student-athletes responded to questions related to their past-30-day use of alcohol, tobacco, marijuana, and prescription drugs. Findings suggest that polysubstance use differs significantly by gender, race, season status, and athletic division. Although a majority of college student-athletes do not engage in polysubstance use, it is reported more frequently for alcohol and tobacco, and alcohol and marijuana. Due to serious consequences associated with polysubstance use, practitioners should consider expanding prevention and treatment efforts to address polysubstance use.