Background/Aims: Standard dose therapy with pegylated interferon α-2a (Peg-IFNα-2a) and ribavirin is not suitable for all patients because of the side effects. This study aims to evaluate the virological responses of low-dose but long-course Peg-IFNα-2a therapy compared with standard therapy. Methodology: Ninety patients with chronic hepatitis C were divided into three groups according to their tolerance to Peg-IFNα-2a. The courses of treatment were 96 or 48 weeks respectively in patients with HCV genotypes 1b or 2a in the 67.5μg and 90μg groups, and were 48 or 24 weeks in the 180μg groups. Serum HCV RNA was quantified to determine RVR, EVR, SVR and ETR. Results: There were no statistical differences in HCV RNA load, HCV genotype at the baseline of the three groups (p>0.05). The rates of RVR, EVR, SVR and ETR (no significant differences in each group), were 63.04%, 82.61%, 71.74% and 85.87% in all 92 patients. Genotype 1b (95% CI=11.97-82.89; p=0.0075) and RVR (95% CI=0.12-0.53; p<0.001) were important predictors of SVR. Conclusions: Patients with low-dose but long-course Peg-IFNα-2a therapy had similar virological responses compared to those with standard therapy. HCV genotype and RVR were independent predictors of SVR.