The Chronic Liver Disease Questionnaire (CLDQ) measures the impact on quality of life of chronic liver diseases, regardless of underlying etiology. The aim of this study was to develop a Spanish version of the CLDQ, and to assess its acceptability, reliability, validity, and sensitivity to change. The forward and back-translation method by bilingual translators, with expert panel and pilot testing on patients, was used for the adaptation. The final version was self-administered, together with the Short Form-36 Health Survey (SF-36), on 149 consecutive patients with chronic liver disease. Child-Turcotte-Pugh scores were evaluated by a physician. To assess reproducibility and responsiveness the CLDQ was readministered to a subsample of stable patients and to those who had received a liver transplant. Validity was evaluated via exploratory factor analysis, the CLDQ pattern across severity groups, and correlation coefficients with “itching” and SF-36 scores. Cronbach's alpha and Intraclass Correlation Coefficient for CLDQ global score were 0.93 and 0.90, respectively, demonstrating good reliability. Validity was supported by correlations of the CLDQ with SF-36 and “itching,” and CLDQ severity gradient (global score means were 5.5, 5.2, 5.0, and 4.5 in patients with no cirrhosis, cirrhosis Child-Turcotte-Pugh A, B, and C, respectively; P = 0.012). Responsiveness was shown by a high CLDQ improvement in patients who had received liver transplant (mean change = −1.4; P < 0.001). In conclusion, the Spanish CLDQ is reliable, valid, responsive, and equivalent to the original. These findings support its use as a standard outcome for patients with chronic liver diseases within the whole severity range, from “no cirrhosis” to transplant recipients, both in Spanish and international studies. Liver Transpl 12:95–104, 2006. © 2005 AASLD.