OBJECTIVE: The Bureau of National Health Insurance in Taiwan implemented an experimental plan for strengthening the chronic hepatitis C patient treatment on October 1, 2003. The purpose of this study was to analyze the medical cost (including direct cost and indirect cost) and Health-Related Quality of Life (HRQoL) during the period of treatment with different treatment strategies (peginterferon versus interferon), from the societal perspective. METHODS: We used a cross-sectional survey method to interview 45 patients with chronic hepatitis C and were receiving treatment in an academic medical center. The medical expenditures were provided by the hospital and the personal expenses reported by patients. The HRQoL questionnaire contained the Short Form-12 (SF-12), the Fatigue symptom inventory (FSI), and the Hospital Anxiety and Depression Scale (HADS). RESULTS: The total medical costs per month for insurance claims was NT$23,666 for peginterferon group and NT$14,125 for interferon. Indirect cost of Peginterferon group is NT$1618, and NT$77 for interferon. Mean scores for PCS was 40.26 and 39.58 in the MCS of the SF-12. Patients' quality of life was lower than that of general people during the treatment. In addition, patients during treatment were worse in fatigue intensity, duration, and interference with quality of life. The same results were observed in the anxiety and depression status. Patients with peginterferon were significantly worse than those on interferon in MCS of SF-12, duration of FSI, and depression of HADS. CONCLUSIONS: We suggest that the genetic type of virus should be identified before the treatment is given. This may let patients receive more appropriate care and also let the health insurance allocate the resource better.