OBJECTIVE: To establish the clinical prognosis, costs and cost-effectiveness of peginterferon alfa-2a (180 mcg/week) plus ribavirin versus no treatment in patients with CHC and PNALT from a Spanish national healthcare system (NHS) perspective. METHODS: A Markov model was developed to simulate the disease progression of 45-year old patients with CHC and PNALT. Fibrosis progression rates in PNALT were obtained from published studies. Efficacy, in terms of sustained virological response (SVR), for peginterferon alfa-2a plus ribavirin and no treatment in patients with genotype 1 and genotype 2/3 was obtained from a multinational, randomized, controlled trial. In this trial, no patients in the control arm achieved an SVR. Transition probabilities and quality of life estimates were obtained from published literature. Unit costs were obtained from a Spanish database. The discount rate employed was 3,5%. RESULTS:In genotype 1 patients, peginterferon alfa-2a plus ribavirin compared with no treatment increases patientxs life expectancy by 0.63 years (0.70 quality-adjusted life years (QALYs)), yielding an incremental cost-effectiveness ratio (ICER) of 14,729 €/ life year gained (LYG) (13,388 €/QALY). In genotype 2/3 patients, peginterferon alfa-2a plus ribavirn increases life expectancy by 1.14 years (1.26 QALYs), yielding an ICER of 109 €/ LYG (99 €/QALY). The overall ICER based on the genotype distribution in the trial is 11,374 €/ LYG (9,952 €/QALY). CONCLUSIONS: From the Spanish NHS perspective, peginterferon alfa-2ª (40KD) (PEGASYS®) plus ribavirin (COPEGUS®) in patients with CHC and PNALT is a cost-effective treatment option, regardless of HCV genotype.