Background/Aims The care cascade for hepatitis C virus (HCV) infection is impeded by multiple barriers, including suboptimal anti-HCV testing, link to care, and diagnosis. We explored the changes in the care cascade of HCV for the past 20 years and its current status in a large cohort from a tertiary referral center. Methods We analyzed 1,144,468 patients who had anti-HCV testing between January 2001 and June 2020. Metrics related to the care cascade of HCV infection and the long-term prognosis of patients were explored. Results The seroprevalence of anti-HCV positivity was 1.8%, with a recent decreasing trend. In all, 69.9% of anti-HCV positive patients performed HCV RNA testing, with a 65.7% positivity. Patients who did not have HCV RNA testing were older and more likely to have a non-hepatocellular carcinoma malignancy, normal alanine aminotransferase level, and good liver function. Linkage times for HCV RNA testing from the anti-HCV positivity and for antiviral treatment from HCV diagnosis decreased, notably after 2015, when highly efficacious oral antiviral treatment was introduced to Korea. The average treatment uptake rate was 35.4%, which increased to 38.9% after 2015. Of the 5,302 patients analyzed for long-term prognosis, the annual incidences of hepatocellular carcinoma were 1.02 or 2.14 per 100 person-years in patients with or without a sustained virological response, respectively. Conclusions The care cascade of HCV infection has been suboptimal for the past 20 years, despite the recent changes. More effort should be made to increase HCV RNA testing and treatment uptake.