Background: Understanding the role that medical use of prescription drugs plays in nonmedical use of prescription drugs can inform prevention efforts. In order to understand fully the potential risk that medical use of prescription drugs conveys for nonmedical use of prescription drugs, the current study explored (a) the simultaneous associations between the medical use of several classes of prescription drugs with current nonmedical use of the same and other prescription drug classes, and (b) whether the associations depended upon past or current medical use. Methods: Data came from a cross-sectional survey of 1686 college students, which assessed past and current medical use and current nonmedical use of stimulants, sedatives/anxiolytics, and opioid analgesics. Results: Logistic regression analyses revealed that both past and current medical use of sedatives/anxiolytics and opioid analgesics predicted the current nonmedical use of the same drug class, whereas past medical use of stimulants predicted the current nonmedical use of stimulants. In addition, current medical use of stimulants predicted current nonmedical use of sedatives/anxiolytics and past medical use of sedatives/anxiolytics predicted current nonmedical use of opioid analgesics. Conclusions: This study provides a broader examination than past research of simultaneous same-drug class and cross-drug class associations between medical and nonmedical prescription drug use, as well as the role of past and current medical use in these associations. Overall, the results suggest that efforts to prevent nonmedical use of a prescription drug class should move beyond targeting only those who have or who are using the same drug class medically.