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Objective To compare the efifcacy of peginterferon alfa-2a (PEGASYS) plus ribavirin (RBV) with interferon alfa-2a plus RBV, and evaluate the safety. Methods Total of 117 patients with chronic hepatitis C were enrolled to receive either PEGASYS (135 μg or 180 μg) subcutaneously once per week, plus RBV (800 mg-1 200 mg) per day for 48 weeks (79 patients, PEGASYS group), or 5 million units of interferon alfa-2a subcutaneously every other day, plus RBV as above dosage for 48 weeks (38 patients, IFNα group). Results Sixty-three of 79 (79.7%) patients reached sustained virological response (SVR) in PEGASYS group, while 14 of 38 (36.8%) patients reached SVR in IFNα group. PEGASYS group was associated with a higher rate of virologic response than IFNα group at week 4, 12, 36, 48 and week 72. Sustained normalization of serum ALT concentrations at week 36, 48 and week 72 was also more common in PEGASYS group than in IFNα group. Baseline levels of ALT and HCV RNA had no effect on SVR in either PEGASYS group or IFNαgroup. Both groups were similar in the frequency and severity of adverse events. Conclusions PEGASYS plus RBV produced similar adverse events but higher rate of SVR. Meanwhile, complications should be prevented and treated promptly in order to increase compliances and effects.