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Background and Aims: In patients with chronic hepatitis C, therapy is considered effective when the sustained virological response (SVR) (undetectable HCV-RNA in serum 6 months after the end of therapy) is achieved. Although the persistence of HCV eradication in short or medium-term period (3–5 years) is well-established, little is known about the long-term follow-up. The aim of the study was to evaluate the long-term persistence of HCV eradication in patients with chronic hepatitis C (CHC) who obtained SVR. In particular, we wanted to assess the risk of longterm virological relapse and liver related-complications. Methods: From January 1989 to April 2008, 150 consecutive subjects (M/F 100/50, median age 47.69 years, range 22–67) with CHC and SVR after interferon-based therapy, were enrolled in a long-term clinical follow-up study. 137 patients had pre-treatment diagnosis of CHC and 13 patients had cirrhosis. All patients received interferon-based therapy (66 with conventional IFN-monotherapy, 25 with conventional IFN and ribavirin, and 59 with pegylated IFN and ribavirin). The patients were followed with clinical, biochemical, virological and ultrasonographic assessments every 6 months until the 3 year of follow-up and than every 12 months. HCV-RNA assessment in serum was determined by quantitative RT-PCR (cut-off