Introduction: Since 2001, the Network for Epidemiology and Information in Nephrology (REIN) has been responsible for the epidemiological monitoring and management of end-stage chronic kidney disease (ESCD) in France. Knowledge of health-related quality of life (QOL) indicators is essential for better understanding the areas affected by the disease and thus proposing appropriate measures aimed at improving patients’ ability to live with their condition. In this context, two cross-sectional studies aimed at estimating the level of health-related QoL among E-CRF patients were conducted in 2005 (dialysis survey) and 2007 (transplant survey) on a sample of French patients, and then repeated in 2011. The objective of this article is to compare these studies and analyze changes in QoL among patients with CRF between these two surveys. Methods: The studies were conducted on a representative sample of subjects aged 18 years and older who were on dialysis (regardless of dialysis modality) or who had a functional kidney transplant for at least one year, and who were followed at a dialysis and/or transplant center in one of the eight selected French regions. Data collection was performed using self-administered questionnaires mailed to patients’ homes. QoL was measured using a generic questionnaire, the MOS SF36, and two specific questionnaires: the short version of the KDQoL (Kidney Disease Quality of Life) for dialysis patients and the ReTransQol V2 (RTQ V2) for transplant recipients. Changes in scores were measured using multivariate analyses, propensity score calculation, and weighting to account for differences in patient profiles between survey periods. Results: QoL declined slightly between 2005–2007 and 2011, regardless of the questionnaire used (generic or specific). However, only a few dimensions were affected, with 2 or 3 domains per measurement tool. For the MOS SF36, the dimensions "general health," "physical pain," and "social life and relationships" decreased significantly (-3.2, -3.7, and -3.8 points). For the specific questionnaires, the "treatment" dimension of the RTQ V2 is the most affected (-2.5 points), as well as the "symptoms/problems" dimension of the KDQoL (-2.4 points). The variation in QoL scores is generally not significant, ranging from -1.6 to -3.8 points for the largest decrease, depending on the statistical methods used. This decrease remains below the 5-point threshold considered clinically significant. Conclusion: QoL among dialysis and transplant patients declined slightly between 2005–2007 and 2011, though this change was not clinically significant.