ABSTRACT. Examined is the relationship of patient-reported health-related quality of life (HRQOL) to the mode of survey administration in the Hemodialysis Study. In addition to self-administered surveys to assess HRQOL, interviewer-administered surveys were made available to include patients with poor vision, decreased manual dexterity, or strong preference. For examining the predictors of participation by self-administration of the survey, multiple logistic regression was performed. For examining the relationship of HRQOL results to mode of survey administration, adjusted differences between the self-administered and interviewer-administered groups were obtained from multiple linear regression models accounting for sociodemographic and case-mix factors. A total of 978 of the first 1000 subjects in the Hemodialysis Study completed the survey by interview (n = 427) or by self-administration (n = 551). The interviewer-administered group was older, was more likely black, had longer duration of ESRD, had a higher prevalence of diabetes, and had more severe comorbidity (all P < 0.01). After adjustment for these differences, patients in the interviewer-administered group had higher scores on scales that measured Role-Physical, Role-Emotional, and Effects of Kidney Disease (all P < 0.001). Dialysis studies that restrict HRQOL measurement to patients who are able to complete surveys without assistance will not accurately represent the health of the overall hemodialysis population. Clinical studies and clinical practices using HRQOL as an outcome should include interviewer administration or risk a selection bias against subjects with older age, minority status, and higher level of comorbidity. Future investigation should include research of survey modalities with a low response burden such as telephone interview, computer-assisted interview, and proxy administration.