The aim of the present study is to examine psychometric properties such as internal consistency reliability and construct validity of the Greek CLDQ. A sample of 366 eligible patients with chronic liver disease (CLD) self-administered the Greek version of the SF-36 Health Survey, the Chronic Liver Disease Questionnaire (CLDQ), and questions on sociodemographic status and treatment. Child Pugh Score was also collected. Hypothesized scale structure, reliability (Cronbach's alpha), and construct validity (convergent, discriminant, and known groups) were assessed. Multitrait scaling confirmed scale structure of the CLDQ with good item convergence (100%) and discrimination (84.1%) rates. Cronbach's alpha rated >0.70 for all scales. Spearman's correlations between the CLDQ and SF-36 scales assessing similar health-related quality of life dimensions were strong ranging above 0.70 (P < 0.0001). Construct validity was confirmed with satisfactory results for known-group comparisons. Most CLDQ scales discriminated significantly between patients according to disease severity, whereas all CLDQ scales discriminated between treatment receivers and nonreceivers. The overall psychometric results for the Greek version of the CLDQ confirmed it as a reliable and valid questionnaire.