Prescription drug misuse (PDM) is a well-documented trend among college students, with a rising prevalence in recent years. Motivations for PDM are an important aspect of the dynamics surrounding this behavior. Using a sample of undergraduate students taken from a large southern university ( N = 841), this study separates users based on their motives into typologies of instrumental, recreational, or mixed motive users and examines the differences between them using a number of social learning, social control, and strain-based risk factors while also comparing them with non-users. The results show that social learning risk factors, specifically those related to the concepts of differential association and differential reinforcement, as well as the use of other drugs, exert the greatest impact on likelihood of PDM between the motivational typologies.