As part of creating a pediatric ESRD-specific Health-Related Quality of Life (HRQOL) assessment instrument, we established pilot data with the PedsQL 4.0 Generic Core Scales in 96 pediatric patients with ESRD receiving hemodialysis (HD), peritoneal dialysis (PD) or with a renal transplant (TX). Patient age ranges were: 2-4 (8; PD n=3, TX n=5), 5-7 (12; HD n=9, TX n=3), 8-12 (25; HD n=5, PD n=6, TX n=14), 13-18 (51; HD n=18, PD n=10, TX n=23). PedsQL ESRD data were compared to healthy children (n=131 child report; n=145 parent report) and across HD/PD/TX. For all domains, ESRD patient HRQOL scores were significantly lower than healthy controls. Transplant patients reported better physical and psychosocial health than dialysis patients. No difference was noted between HD and PD patients for any PedsQL domain. Our data demonstrate that the PedsQL 4.0 Generic Core Scales is a useful measurement instrument to screen for HRQOL impairment in pediatric patients with ESRD. We suggest that the ESRD-specific HRQOL instrument in development is needed to help define condition-specific HRQOL differences between modalities.