Subjective symptom assessment should be a fundamental component of health-related quality of life (HRQL) assessment in end-stage renal disease (ESRD). Unfortunately, no symptom checklist has established reliability or validity in ESRD. We report the validation of a modified Edmonton Symptom Assessment System (ESAS) in 507 dialysis patients who concurrently completed the Kidney Dialysis Quality of Life-Short Form (KDQOL-SF) questionnaire. The ESAS demonstrated a mean of 7.5+/-2.5 symptoms. The symptoms reported as most severe were tiredness, well-being, appetite, and pain. The overall symptom distress score was strongly correlated with the KDQOL-SF subscales symptom/problem list (r=-0.69, P<0.01), effects of kidney disease (r=-0.52, P<0.01), and burden of kidney disease (r=-0.50, P<0.01), as well as lower RAND-12 physical health composite (PHC) (r=-0.54, P<0.01) and lower RAND-12 mental health composite (MHC) (r=-0.62, P<0.001). In the multivariate regression analysis, after controlling for potential confounding variables including comorbidity using the modified Charlson Comorbidity Index, the ESAS symptom distress score remained strongly associated with the MHC (slope=-0.82+/-0.07, P<0.01) and PHC (slope=-0.48+/-0.07, P<0.01). The ESAS symptom distress score accounted for 29% of the impairment in PHC and 39% of the impairment in MHC. The intraclass correlation coefficient for the total symptom distress score in a 1-week test-retest was 0.70, P<0.01. Symptom burden is high and adversely affects HRQL in dialysis patients. The modified ESAS is a reliable, valid, simple, and useful method for regular symptom assessment in this patient population.