Background: Peginterferon alfa-2b (12-kDa) has a slower rate of clearance and a longer half-life than conventional interferon alfa-2b.  Better efficacy of peginterferon alfa-2b has been shown in western studies. Objective: To study the efficacy and safety of peginterferon alfa-2b plus ribavirin with interferon alfa-2b plus ribavirin therapy in Thai patients with chronic hepatitis C.Patients and Methods: 95 patients with chronic hepatitis C were randomized to receive peginterferon alfa-2b 1.5 (g/kg (Maximum 100 ug) subcutaneously once a week plus ribavirin 800-1,000 mg/day orally or interferon alfa-2b 3MU three times a week plus ribavirin 800-1,000 mg/day for 48 weeks.  All patients were assessed at week 72 for a sustained virological response (SVR), defined as an undetectable HCV RNA by PCR (<100 copies per milliliter).Results: The SVR rates between peginterferon/ribavirin group and interferon/ ribavirin group were not significantly different, 27/42 (64.3%) vs 30/51 (58.8%), (P = 0.67).  In patients receiving at least 80% of treatment medications and duration of treatment, the SVR rates increased to 85.3% (29/34) in peginterferon group and 71.4% (30/42) in interferon group.  Peginterferon plus ribavirin achieved higher SVR in genotype 1, 6 than interferon plus ribavirin (83.3% VS 55%), P = 0.089). Both treatment groups had good SVR (75%) in genotype 2, 3 and were respectively similar to the frequency and severity of adverse events, which were typical in those associated with interferon alfa and ribavirin.Conclusion: Peginferon alfa-2b once weekly plus ribavirin is more effective than conventional interferon alfa-2b thee times weekly plus ribavirin in patients infected with HCV genotype 1, 6