Background: Pegylated interferon and ribavirin combination therapy remain the first-line treatment for chronic hepatitis C virus (HCV) infection. In contrast to the large number of studies in treatment-naive patients, the effectiveness of retreatment in patients who have previously failed pegylated interferon based therapy is not much reported. Objectives: The aim of this retrospective study was to focus on the efficacy of pegylated interferon alpha and ribavirin in retreated chronic hepatitis C patients. Patients and Methods: All patients were treated with pegylated interferon alpha either 2a (180 mu g) or 2b (1.5 mu g/kg) subcutaneously once weekly for a 48week period, plus ribavirin 1000-1200 mg/day. The patient who had a negative HCV RNA at the end of 48 weeks were followed up for 24 weeks, and the patients who relapsed in the post-treatment follow-up period of 24 weeks were treated again with pegylated interferon alpha; but if the first treatment was administered with pegylated interferon alpha 2a, the second was administered with pegylated interferon alpha 2b and if pegylated interferon alpha 2b, then the second with pegylated interferon alpha 2a. Results: We evaluated the outcome of our patients with chronic HCV who achieved a viral response at the end of the therapy, but did not achive sustained virologic response; 54% (38/70) of patients did achieve sustained virologic response, while 46% (32/70) of patients did not (eight patients did not achieve early virologic response, five patients were nonresponders at 24th week of the treatment, the remaining 19 patient had negative HCV at the end of the therapy but did not achieve sustained virologic response). We began from 19 patients to 8 patients, who had negative HCV RNA at the end of the treatment, but did not achieve sustained virologic response, interferon plus ribavirin therapy again. If the patient had interferon alpha 2a, we gave in the second tour alpha 2b; and if alpha 2b, then alpha 2a. The early virologic response of these nine patients were found to be 63% (5/8). These 5 patients who had rapid virologic response and early virologic response at the second therapy achieved sustained virologic response this time. Conclusions: These findings suggest that the standard 48-week treatment is insufficient and that an extended course of treatment may be necessary. Relapse is a poorly understood clinical outcome in the treatment of chronic HCV patients. Retreament can give a chance to some patients specially who have early virologic response and negative HCV RNA at the end of the first therapy.