Background and Objective: Cases of acute Hepatitis C Virus (HCV) increased approximately 3.8-fold between 2010 and 2017 due, in part, to increasing injection drug use and surveillance. Furthermore, multiple HIV outbreaks in Europe and North America have been attributed to injection drug use. Emergency departments are uniquely situated to address infections among people using opioids given their limited utilization of other healthcare resources. This review assesses prevalence, testing history, and potential benefit for screening of HIV and HCV among patients presenting to emergency departments following an opioid overdose. Methods: 134 emergency department encounters at an academic medical center in the central United States representing 120 unique patients diagnosed with poisoning by opioids between January 2021 and May 2022 were included in the analysis. Emergency department and most recent primary care visit notes, as well as laboratory results from January 2000 to May 2022 were reviewed for history of HIV and HCV testing and viral load. Results: 48 patients (40%) had a history of HCV testing and 54 (45%) had a history of HIV testing. 20 patients had tested positive for HCV (41.6% of tested, 16.7% of total), and 1 had tested positive for HIV (1.9% of tested, 0.8% of total). 8 patients had detectable HCV viral loads, 6 were virologically suppressed, and 6 had no documented quantitative testing. 1 patient had a detectable HIV viral load. Conclusions: There is a substantial burden of HCV among individuals presenting to American emergency departments following opioid overdoses. Universal HCV screening for individuals being observed following an overdose could detect many undiagnosed HCV infections. These results have been reported to the state government which plans to implement a program to test all emergency department patients suspected of opioid abuse for HCV and to coordinate treatment for those who test positive.