A health-related quality of life (HRQOL) assessment is particularly necessary for patients with chronic venous insufficiency (CVI), as is an assessment of the objective signs (edema, dilated veins, ulceration and other lesions). A comprehensive 3-year research program was undertaken in France to construct and validate the Chronic Venous Insufficiency Questionnaire (CIVIQ), a questionnaire designed specifically to evaluate the quality of life for CVI sufferers. The next step was to implement a program of cross-cultural validation in several countries. Translation into Spanish was undertaken following international guidelines. Face validity was verified with a pilot test among 12 Spanish patients. Psychometric validation was performed in Spain (n = 476 patients with CVI). The Spanish CIVIQ demonstrated very good internal consistency, high reproducibility and responsiveness, as well as longitudinal clinical validity. It appears to be a valuable instrument for assessing improvement in patient quality of life in response to both therapy in clinical practice and clinical trials.