A proportion of chronic hepatitis C patients who were treated with interferon have a sustained normalization of transaminase levels after interferon therapy without hepatitis C virus (HCV)-RNA clearance. We determined their clinical characteristics and long-term outcome in relation to progression to liver cirrhosis (LC) and the development of hepatocellular carcinoma (HCC). A total of 250 patients with chronic hepatitis C who were treated with interferon were studied for 8 to 11 years' posttherapy. Sixty-seven patients (27%) were complete responders with clearance of HCV RNA. Twenty-six (10%) were biochemical responders who had sustained normal alanine transaminase (ALT) levels without viral clearance. The remaining patients were short-term responders (n = 70) and nonresponders (n = 87). Biochemical responders were older, had higher levels of pretreatment HCV RNA in serum than complete responders, and had less advanced liver histology than nonresponders. Histologic grading scores decreased significantly at the end of therapy, while the staging scores did not change significantly. The annual incidence of cirrhosis was 0% in biochemical and complete responders, which was significantly lower than nonresponders and the controls (P = .0001). The annual incidence of HCC was 0.37% in complete responders and 0.50% in biochemical responders, which was significantly lower than nonresponders (P = .0001 for both). Our findings suggest that biochemical responders had high pretreatment viral levels with less advanced liver histology, and their long-term outcome appeared to be good irrespective of the persistence of the virus.