Timely and specific drug detection is critical for an effective clinical and population-level health system response to potentially fatal drug exposures. In the United States, drug surveillance systems are months or even years behind the monitoring of health outcomes associated with dangerous increases in drug exposure. Novel approaches to early warning drug detection systems are urgently needed. Wastewater pharmacoepidemiology is an emerging field facilitating the study of population drug use through the analysis of environmental samples obtained from wastewater distribution systems. In the feasibility study, we sampled wastewater from multiple locations at various time points flowing from Ben Hill Griffin Stadium in Gainesville, FL during two football games in 2016, October (Florida vs. Missouri) and November (Florida vs. South Carolina). Utilizing liquid chromatography-tandem mass spectrometry (LC-MS/MS), we tested for over 40 drugs and drug metabolites in the wastewater samples. The initial results of the drug analyses revealed the presence of ethyl glucuronide, an ethanol metabolite, as well as cocaine, cocaethylene and benzoylecgonine in several of the wastewater samples. In the future, to enhance the detectability of drug analytes in the wastewater, samples will be subjected to hyperconcentration. In addition, we plan to expand the scope of testing to include a wide variety of licit and illicit drugs, and conduct pilot microbiome studies. This work represents a unique collaboration between the Department of Health Outcomes and Policy, the Department of Pathology, Immunology and Laboratory Medicine, UF Physical Plant Division, UF Utilities and Energy Services, and the University Athletic Association.