Hepatitis C virus genotype and viral loads are important predictors for sustained virologic response (SVR) to interferon-alpha therapy for chronic hepatitis C (CHC). We have conducted a prospective study on treatment of 90 patients with a tailored-dose and extended interferon-alpha regimen according to pretreatment virologic factors (low-risk, genotype non-1b/viral loads≤0.65 Meq./ml, 6 million units thrice weekly for 12 weeks (6 MU×12 weeks) followed by 3 MU×24 weeks; high-risk, genotype 1b/viral loads>0.65 Meq./ml, 6 MU×24 weeks followed by 3MU×24 weeks; medium-risk, the others, 6MU×12 weeks followed by 3 MU×36 weeks), and compared to 123 patients with fixed-dose regimen (6 MU×24 weeks). Patients with tailored-dose regimen had a significantly higher rate of SVR than those receiving fixed-dose interferon-alpha (46.7% versus 29.3%, P<0.01, intention-to-treat analysis). Improved efficacy was mainly seen in the medium-risk (48.9% versus 26.6%, P=0.02) and the high-risk groups (26.1% versus 8.3%, P=0.06), but not in the low-risk group. By using multivariate logistic regression, low pretreatment viral loads and tailored-dose IFN regimens were significantly associated with higher SVR in both the high- and medium-risk groups. There were no differences in the tolerability and in the incidence of adverse effects between fixed-dose and tailored-dose groups. In conclusion, our results demonstrate the efficacy of tailored-dose interferon-alpha therapy for CHC; these could provide decision-making information for standard/pegylated interferon-alpha combining ribavirin therapy according to baseline predictors.