Objectives: This study assesses students' non-medical use of prescription drugs (NMUPD) from college entrance to graduation, and examines factors that predict NMUPD. Participants: The study was conducted between May 2011 and September 2015 with 338 students. Methods: Longitudinal cohort study design was used to examine NMUPD across time, and NMUPD-related attitudes and subjective norms. Five yearly interviews were conducted to collect data. Cox proportional hazards regression analysis was used to examine time to NMUPD. Results: Thirty-five percent of study participants reported NMUPD; the majority of those initiated non-medical use before their third year in college. Analyses indicated that more positive attitudes towards NMUPD (HR = 1.73, p < 0.001), increased subjective norms regarding NMUPD (HR = 1.01, p < 0.01), and gender (male) (HR= 1.89, p < 0.001) were significantly associated with sooner NMUPD. Conclusions: Findings suggest that NMUPD prevention efforts that target mutable factors such as attitudes and subjective norms should be implemented early during students' college careers.