The benefit of extending treatment duration with peginterferon (PEG-IFN) and ribavirin (RBV) from 48 weeks to 72 weeks for patients with chronic hepatitis C genotype 1 infection has not been well established. In this prospective, international, open-label, randomized, multicenter study, 1,428 treatment-naΔ± Β¨ve patients from 133 centers were treated with PEG-IFN alfa-2b (1.5 lg/kg/week) plus RBV (800-1,400 mg/day). Patients with detectable hepatitis C virus (HCV) RNA and a !2-log 10 drop in HCV RNA levels at week 12 (slow responders) were randomized 1:1 to receive 48 weeks (n 5 86) or 72 weeks (n 5 73) of treatment. Sustained virologic response (SVR) rates were 43% in slow responders treated for 48 weeks and 48% in slow responders treated for 72 weeks (P 5 0.644). Relapse rates were similar in slow responders treated for 48 or 72 weeks (47% versus 33%, P 5 0.169). The safety profile was similar in both treatment arms; serious adverse events leading to discontinuation of treatment were observed in 3.5% of slow responders treated for 48 weeks and 8.2% of those treated for 72 weeks. Among slow responders with a <2-log drop in HCV RNA at week 8, SVR was 39% in the 72-week arm and 19% in the 48-week arm. Conclusion: These data suggest that 48 weeks of therapy with PEG-IFN alfa-2b plus RBV (800-1,400 mg/day) should remain a standard-of-care treatment for treatment-naΔ± Β¨ve G1 slow responders.