OBJECTIVES: The prevalence of hepatitis is high in emergency department (ED) attendees in the United Kingdom, with a prevalence of up to 2% for hepatitis B (HBV) HBsAg, and 2.9% for hepatitis C (HCV) RNA. The aim of this paper is to perform an economic evaluation of opt-out ED-based HCV and HBV testing. METHODS: A Markov model was developed to analyze the cost-effectiveness of opt-out HCV and HBV testing in EDs in the UK. The model used data from UK studies of ED testing to parameterize the HCV and HBV prevalence (1.4% HCV RNA, 0.84% HBsAg), test costs, and intervention effects (contact rates and linkage to care). For HCV, we used an antibody test cost of £3.64 and RNA test cost of £68.38, and assumed direct-acting antiviral treatment costs of £10 000. For HBV, we used a combined HBsAg and confirmatory test cost of £5.79. We also modeled the minimum prevalence of HCV (RNA-positive) and HBV (HBsAg) required to make ED testing cost-effective at a £20 000 willingness to pay per quality-adjusted life-year threshold. RESULTS: In the base case, ED testing was highly cost-effective, with HCV and HBV testing costing £8019 and £9858 per quality-adjusted life-year gained, respectively. HCV and HBV ED testing remained cost-effective at 0.25% HCV RNA or HBsAg prevalence or higher. CONCLUSIONS: Emergency department testing for HCV and HBV is highly likely to be cost-effective in many areas across the UK depending on their prevalence. Ongoing studies will help evaluate ED testing across different regions to inform testing guidelines.