OBJECTIVES: To estimate the cost-effectiveness of treating interferon-naïve CHC patients with peginterferon alfa-2a (180 mcg/week) plus ribavirina (1200 mg/day) early before progression to more advanced disease. METHODS: A published Markov lifetime model was used to estimate the costs and benefits associated with early versus delayed treatment for HCV. The target population consisted of treatment-naive HCV-1 patients with mild liver disease. The interventions were either early treatment or regular monitoring (delayed treatment) for evidence of progression to moderate or cirrhosis stage. Fibrosis progression rates came from published longitudinal cohort studies. The analysis was conducted from the perspective of the Italian NHS. Life Years Gained (LYGs) were considered, as well as Quality-Adjusted Life-Years (QALYs) and direct medical costs. LYGs and QALYs were based on the results of an international clinical trial. Benefits and costs were discounted at 3%. Sensitivity analyses were performed. RESULTS: Early treatment is expected to reduce the risk of cirrhosis at 30 years by 13.5% (23.7% early vs. 37.2% delayed), to increase mean overall survival by 0.48 years (29.77 LY early vs. 29.29 LY delayed) and to increase mean survival adjusted for quality of life by 0.75 years (14.83 QALY early vs. 14.08 QALY delayed). The expected cost (per patient) is €27,313.26 with early treatment and €22,965.37 with regular monitoring. The study calculated for early treatment versus delayed treatment the incremental cost per life year gained and per QALY gained. It was €9114.16 and €5823.92, respectively. Sensitivity analyses showed that age and social discount rate are the most influential parameters. CONCLUSION: Early treatment with peginterferon alfa-2a (40KD) plus ribavirin of CHC when this is at a mild stage is expected to reduce risk of cirrhosis, to increase life expectancy, and to be cost-effective when compared with monitoring for evidence and subsequent treatment of advanced disease.