Clinical outcomes of chronic hepatitis C infection in patients with advanced fibrosis include liver failure, hepatocellular carcinoma, and death. To investigate whether sustained virologic response to treatment for hepatitis C is associated with improved clinical outcomes. Retrospective cohort study. 5 hepatology units of tertiary care centers in Europe and Canada caring for patients with chronic hepatitis C treated between 1990 and 2003. Consecutively treated patients with chronic hepatitis C who had biopsy-proven advanced fibrosis or cirrhosis (Ishak score, 4 to 6). Sustained virologic response, defined as absence of detectable hepatitis C virus RNA at 24 weeks after the end of treatment, and clinical outcomes, defined as death (liver-related or non-liver-related), liver failure, and hepatocellular carcinoma. Of 479 patients, 29.6% had sustained virologic response and 70.3% did not. Median follow-up was 2.1 years (interquartile range, 0.8 to 4.9 years). Four patients with and 83 without sustained virologic response had at least 1 outcome event. Sustained virologic response was associated with a statistically significant reduction in the hazard of events (adjusted hazard ratio, 0.21 [95% CI, 0.07 to 0.58]; P = 0.003). The effect was largely attributable to a reduction in liver failure, which developed in no patients with and 42 patients without sustained virologic response (5-year occurrence, 0% vs. 13.3% [CI, 8.4% to 18.2%]; unadjusted hazard ratio, 0.03 [CI, 0.00 to 0.91]). Because few events occurred in the sustained virologic response group, the study had limited ability to detect differences between groups in individual outcomes. In addition, the study was retrospective; selection and survival biases may therefore influence estimates of effect. Sustained virologic response to treatment is associated with improved clinical outcomes, mainly prevention of liver failure, in patients with chronic hepatitis C and advanced fibrosis.