The Choices for Healthy Outcomes in Caring for End-Stage Renal Disease ([ESRD] CHOICE) Study was designed to evaluate the effectiveness of alternative dialysis prescriptions. As part of CHOICE, we developed an instrument for measuring health-related quality of life (HRQOL) for patients with ESRD that would complement the Medical Outcomes Study 36-Item Short-Form Survey (SF-36) and be sensitive to differences in dialysis modality (hemodialysis [HD] and peritoneal dialysis [PD]) and dialysis dose. The selection of HRQOL domains to be included was based on: (1) a structured literature review of 47 articles describing 53 different instruments; (2) content analysis of five focus groups with HD and PD patients, nephrologists, and other providers; (3) a survey of 110 dialysis providers about features of different modalities that affect patient HRQOL; and (4) a semistructured survey of 25 patients with ESRD on the effects of dialysis on functioning and HRQOL. To help prioritize domains and items identified by these methods, a representative sample of 136 dialysis patients rated each item for frequency and bother. A panel of nephrologists provided advice about the salience of items to modality or dose. Items and scales were selected with a preference for existing measures tested in patients with ESRD and were tested for reliability and validity. The first four steps yielded 22 HRQOL domains that included 96 items: 8 generic domains in the SF-36 (health perceptions, physical, social, physical and emotional role function, pain, mental health, and energy); 8 additional generic domains (cognitive functioning, sexual functioning, sleep, work, recreation, travel, finances, and general quality of life); and 6 ESRD-specific domains (diet, freedom, time, body image, dialysis access [catheters and/or vascular], and symptoms). New items were developed or adapted to assess ESRD-specific domains. Scales for these items showed adequate internal consistency (Cronbach's alpha > 0.70, except for time [alpha = 0.57] and quality of life [alpha = 0.68]), as well as convergent and discriminant construct validity in a sample of 928 patients. The final questionnaire included 21 domains (time was deleted) and 83 items. We have designed a patient-centered instrument, the CHOICE Health Experience Questionnaire, that addresses domains that may be sensitive to differences in dialysis modality and dose and shows evidence for reliability and validity as a measure of HRQOL in ESRD.