Objective: To examine the association between nonmedical use of over-the-counter medications (NMUOTC) and nonmedical use of prescription drugs (NMUPD). Participants: University students surveyed on NMUOTC and NMUPD between August and December 2011 (N = 939). Methods: Cross-sectional data analysis of online survey. Results: The majority of respondents were women, undergraduate, Caucasian, and not affiliated with Greek life. NMUPD and NMUOTC were reported by 21.4% and 11.2% of students, respectively. NMUOTC was significantly associated with NMUPD in unadjusted analyses and after adjustment for gender, age, race/ethnicity, and Greek membership (odds ratio: 3.37, 95% confidence interval: 2.17, 5.23). Secondary analyses showed a relationship between over-the-counter (OTC) cough medication misuse and NMUPD, OTC stimulant misuse and prescription stimulant misuse, and OTC sleep aid misuse with prescription depressant misuse. Conclusions: Results suggest the importance of both measuring the prevalence of OTC misuse and incorporating its misuse into assessments of polydrug use in the university population.