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Background and Purpose There are no data regarding psychometrically validated, healthrelated quality-of-life instruments designed specifically for patients with multiple sclerosis (MS) in Greece. Recently, the MS International Quality-of-Life questionnaire (MusiQoL), a multidimensional, self-administered questionnaire, which is available in 14 languages (including Greek), has been validated using a large international sample. We investigated the validity and reliability of the Greek version of the MusiQoL. Methods Consecutive patients with different types and severities of MS were recruited from two tertiary-care centers in Greece. All patients completed the MusiQoL, the Short-Form-36 quality-of-life questionnaire (SF-36), and a symptom checklist at baseline and 21±7 days (mean± SD) later. Data regarding sociodemographic status, MS history, and functional outcome were also collected prospectively. Construct validity, internal consistency, reproducibility, and external consistency were tested. Results A total of 92 patients was evaluated. The construct validity was confirmed in terms of satisfactory item-internal consistency correlations and scaling success (87.5-100%) of itemdiscriminant validity. The dimensions of the MusiQoL exhibited high internal consistency (Cronbach’s alpha: 0.63-0.96), and reproducibility was satisfactory (intraclass correlation coefficients: 0.69-0.99). External validity testing indicated that the MusiQoL correlated significantly with all SF-36 dimension scores (Spearman’s correlation: 0.43-0.76). Conclusions The Greek version of the MusiQoL appears to be a valid and reliable instrument for measuring quality of life in Greek MS patients.