Retreatment of chronic hepatitis C patients nonresponders to interferon (IFN) alone with the standard dose of IFN 3 million units (MU) thrice weekly (TIW) plus ribavirin for 24 weeks has yielded low sustained virological response (SVR), averaging 8%. The aim of the present, open‐labelled, randomized study was to evaluate the efficacy of IFN induction therapy followed by prolonged high dose of IFN plus ribavirin in nonresponders. One hundred and fifty‐one patients were randomized to receive 5 MU daily of IFN alfa‐2b (group 1, n = 73) or 5 MU TIW of IFN alfa 2b (group 2, n = 78) for 4 weeks followed by IFN (5 MU TIW) plus ribavirin (1000/1200 mg/daily) for 48 weeks in both groups. In an intention‐to‐treat analysis, the sustained virological response (SVR) at 24‐week follow‐up was 33 and 23% for group 1 and 2, respectively (P = 0.17). The overall SVR was 52 and 18% in patients with genotype 2/3 and 1/4, respectively. Among genotype 1/4 patients the SVR was 29 and 11% for age younger or older than 40 years. Compared with genotype 2/3 patients, the risk (95% confidence interval) of nonresponse to retreatment was 3.0‐fold (1.17–8.0) in younger genotype 1/4 patients and 8.4‐fold (3.0–23.29) in older genotype 1/4 patients. In conclusion these results suggest that retreatment with a reinforced regimen should be focused in nonresponder genotype 2/3 patients and younger genotype 1/4 patients, who are most likely to benefit. Induction therapy does not improve SVR.