Objective: The authors describe the epidemiology of risk behavior associated with poly-drug use in a college bar district of a large campus community. Participants: A total of 469 bar patrons participated in the study. Methods: The authors used self-report data and biological measures collected from patrons outside bars in July and August of 2007. Results: The mean breath alcohol concentration of the exiting patrons was 0.09. Illicit and prescription drug use on the nights of data collection and in the recent past were significant features of the profile of patron risk behavior. About one-quarter of the patrons using only alcohol reported an intention to drive a vehicle within 60 minutes of leaving an establishment, compared with almost one-half of those using both alcohol and marijuana. Conclusions: A substantial amount of high-risk behavior was generated from the bar district on 4 typical nights. College bar districts should be a priority focus for prevention efforts. (Contains 4 figures and 2 tables.)