Background/Aims: The aim of this study is to explore the validity and reliability of the health-related quality of life SF-36 questionnaire in patients undergoing renal replacement therapy. Methods: A multicenter descriptive transversal study was carried out in Galicia, Spain, with patients undergoing renal replacement therapy. The tool used to measure the health-related quality of life was the authorized Spanish version of the ‘SF-36’ generic health questionnaire. The internal consistency of this survey was determined by means of interscale correlations and Cronbach’s α statistic. Validity was examined with a principal component exploratory factor analysis with Varimax rotation. Results: A total of 213 patients waiting for a kidney transplant and 72 recipients with a functioning renal transplant were studied. All the interscale correlations were positive and significant. The overall statistical value for Cronbach’s α was equal to 0.91 (95% CI: 0.91–0.94) and in all domains this value ranged from 0.7 to 0.92. The factor analysis identified 8 factors that explain 66.6% of the variance, 5 of which consisted of the same structure as 5 factors (domains) of the theoretical model. Conclusion: The SF-36 questionnaire is also a reliable and valid tool when used to measure the quality of life of patients undergoing renal replacement therapy.