Background: Emergency Department (ED) viral hepatitis screening programs typically report short-term outcomes. We evaluated the medium-term impact of an ED-based screening for Hepatitis C (HCV), Hepatitis B (HBV), and Hepatitis D (HDV) viruses. Methods: Prospective opportunistic screening conducted between January 2020 and December 2024 at a referral hospital in Barcelona. Adults attending the ED were screened for HBV, HCV, and HDV. Positive cases were evaluated and linked to care when appropriate. To assess screening impact, HCV RNA and HBsAg prevalences were compared between 2020–2021 and 2023–2024 among participants aged ≤80 years. Results: Over five years, 39,532 individuals were screened: 220 (0.56%) had detectable HCV RNA, 234 (0.59%) HBsAg, and 4 HDV RNA. Of 110 patients with detectable HCV RNA eligible for linkage, 84 (76%) were treated and cured. Among 135 HBV-positive individuals eligible for linkage, 116 (86%) attended outpatient follow-up. HCV RNA prevalence significantly decreased (0.58% vs. 0.35%, p = 0.005), whereas HBsAg prevalence did not vary (0.7% vs. 0.58%, p = 0.224). Conclusions: Sustained ED-based screening enabled the identification and linkage to care of several individuals with HBV and HCV. This strategy contributed to a reduction in HCV prevalence among ED attendees and supports opportunistic ED screening in viral hepatitis elimination goals.