OBJECTIVES: Treatment adherence is a key issue in chronic infectious diseases such as Chronic Hepatitis C (CHC). The aim of the study was to develop two valid and feasible disease specific questionnaires to assess adherence to treatment of CHC monoinfected patients and HCV/HIV co-infected patients. METHODS: Questionnaires development was carried out in two phases. In the first phase, a literature review was performed in order to identify factors closely related to treatment adherence. By means of a focus group, disease experts selected the items considered most likely to affect adherence from the initial list, then the chosen items underwent a qualitative analysis and were rephrased to make them suitable for inclusion in a questionnaire. The first version of the questionnaires was completed by 18 patients (8 monoinfected and 10 co-infected) in order to evaluate the comprehension of questions, response categories, questionnaires applicability and the patients’ opinion on the proposed questionnaires design. The questionnaires are currently being validated in the second phase, an ongoing prospective study including 1120 patients. RESULTS: The two questionnaires developed for monoinfected and for co-infected patients contained 11 and 13 questions, respectively. Both questionnaires included two questions related to treatment adherence and questions about reasons of non-adherence. To date 843 patients have been included in the prospective study; 71.9% are male, 77.1% are monoinfected patients, 22.9% co-infected and 63.0% of patients have baseline RNA-HCV > 800.000 UI/ml (62.1% monoinfected and 66.1% co-infected). The HCV genotype distribution is 74.8% G-1/4 and 25.7% G-2/3.  The HIV positive patients receiving ART Therapy are 91.2%. CONCLUSIONS: The two disease specific questionnaires developed to assess adherence to treatment showed feasibility and good comprehension by patients with HCV monoinfection and with HCV/HIV co-infection, respectively. Further validation is ongoing in a prospective study.