Objective: Health-related quality of life (HRQOL) is an important outcome in dialysis care. Previous research has related protein-energy nutritional status to generic HRQOL domains, but it is still not clear as to how it relates to HRQOL domains that are unique to hemodialysis patients. Therefore, our aim was to study the relation between protein-energy nutritional status and kidney disease-specific HRQOL domains in hemodialysis patients. Design: This was a cross-sectional study. Setting: This study was performed at multiple centers. Patients or Other Participants: We evaluated the first 590 hemodialysis patients who had enrolled in the Convective Transport Study. Determinants: We measured protein-energy nutritional status by using the Subjective Global Assessment, albumin, normalized nitrogen appearance, creatinine, body mass index, and cholesterol. Main Outcome Measure: HRQOL was assessed by using the Kidney Disease Quality Of Life-Short Form. Results: In all, 83% of the cohort was found to be well-nourished on the basis of the Subjective Global Assessment. Multiple nutritional parameters were positively related to the physical summary of generic HRQOL and to the following kidney disease-specific HRQOL scales: the effects of the kidney disease on daily life, the burden of the kidney disease, and overall health. Conclusions: This study showed that, even in predominantly well-nourished hemodialysis patients, protein-energy nutritional status was significantly related to kidney disease-specific HRQOL. © 2011 National Kidney Foundation, Inc.