Background: Among patients with chronic HCV treated with pegylated interferon and ribavirin, the highest sustained virologic response (SVR) rates are achieved in patients with a rapid virological response (RVR). Here we investigate how the time taken to become HCV RNA undetectable influences the probability of relapse during untreated follow-up. Methods: Data from 569 patients treated for 48 weeks with peginterferon alfa-2a (40KD) 180µg/week plus ribavirin 1000/1200mg/day were included in the intent-to-treat analysis. Response was classified as RVR, complete early virological response (cEVR) slow responder and non-EVR. Results: There was a correlation between the time required to become HCV RNA undetectable and the relapse rate after stopping treatment. Patients with an RVR had the lowest relapse rate (4%); this increased among patients with slower responses. Conclusion: There was an inverse correlation between the time taken to achieve a virologic response and the probability of relapse. Background: Rapid virologic response (RVR; HCV RNA <50IU/mL) at week 4 of treatment with pegylated interferon plus ribavirin can be used to predict the probability of achieving an SVR. Patients with detectable HCV RNA at week 4 have a lower probability of achieving an SVR than those with an RVR; further subdivision of these patients may be useful in predicting outcomes. Methods: We conducted a retrospective analysis including 569 genotype 1 patients treated for 48 weeks with peginterferon alfa-2a (40KD) 180 g/week and ribavirin 1000/1200 mg/day. Patients were categorized as RVR and non-RVR. Those without an RVR were further subdivided into detectable but unquantifiable, 3, 2, 1 or <1 log10 drop in HCV RNA. The proportion of patients with undetectable HCV-RNA at week 12 and achieving an SVR was calculated within each category. Results: RVR and non-RVR patients had an 88% and 43% rate of SVR respectively. Among non-RVR patients, rates of SVR depended on the categorical response at week 4: detectable but unquantifiable HCV RNA, 77%; 3 log10 drop in HCV RNA, 61%; 2 log10 drop, 43%; 1 log10 drop, 27%; and <1 log10drop, 13%. Independent of week 4 response, undetectable HCV RNA at week 12 was also highly predictive of SVR. Conclusions: Patients achieving an RVR have high rates of SVR. Among patients who do not achieve an RVR a more precise prediction of SVR can be achieved by considering the extent of viral load reduction at week 4 and week 12.