OBJECTIVES: Adherence to the prescribed treatment regimen is an important factor that impacts on the success of therapy in chronic hepatitis C. The aim of this study was to develop a cost-effectiveness analysis of a multidisciplinary support program (MSP) versus conventional treatment in a group of Hepatitis C (HC) patients. METHODS: A total of 278 naïve and mono-infected patients with HC were included in the study: 131 in Group 1 (MSP strategy) and 147 in Group 2 (conventional treatment approach). All patients were treated with Peg-IFN-alfa-2a and Ribavirin. The MSP not only included hepatologists and nurses, but also, pharmacists, psychologists and assistants; additionally uniform patient education, open and flexible visits scheduling, continued evaluation of psychiatric risk and active medication were carried out. A decision-tree model was built to estimate the incremental cost-effectiveness ratio (ICER) of MSP vs. conventional control. Unitary costs of HC drugs and professionals were included. Effectiveness was measured in terms of sustained virological response (SVR), adherence was defined as >80% dose administered. RESULTS: For genotypes 1/4 (G-1/4), adherence was achieved in 92.4% of patients in group 1 and 69.3% in group 2 (p=0.0005), for genotypes 2/3 (G-2/3) adherence was achieved in 96.9% and 93.2% in groups 1 and 2 respectively (p>0.05). SVR differed in the two groups: 66.7% in group 1 and 48.9% in group 2 for G-1/4 (p=0.03) and 87.7% and 81.4% for G-2/3 (p>0.05) for groups 1 and 2 respectively. Cost per SVR was higher in group 2 than in group 1 (€24,079 and €20,197 in G-1/4; €8,351 and €7,723 in G-2/3). The ICER was €9,533/SVR in G-1/4 patients and group 1 was dominant over group 2 in G-2/3 patients. CONCLUSIONS: The MSP could improve the adherence to the HC treatment and therefore the virological response, and could be also a cost-effective strategy compared with the conventional approach.