Purpose: Hemodialysis patients undergo frequent and long visits to the clinic to receive adequate dialysis treatment, medical guidance, and support. This may affect health-related quality of life (HRQOL). Although HRQOL is a very important management aspect in hemodialysis patients, there is a paucity of information on the differences in HRQOL between centers. We set out to assess the differences in HRQOL of hemodialysis patients between dialysis centers and explore which modifiable center characteristics could explain possible differences. Methods: This cross-sectional study evaluated 570 hemodialysis patients from 24 Dutch dialysis centers. HRQOL was measured with the Kidney Disease Quality Of Life-Short Form (KDQOL-SF). Results: After adjustment for differences in case-mix, three HRQOL domains differed between dialysis centers: the physical composite score (PCS, P = 0.01), quality of social interaction (P = 0.04), and dialysis staff encouragement (P = 0.001). These center differences had a range of 11-21 points on a scale of 0-100, depending on the domain. Two center characteristics showed a clinical relevant relation with patients' HRQOL: dieticians' fulltimeequivalent and the type of dialysis center. Conclusion This study showed that clinical relevant differences exist between dialysis centers in multiple HRQOL domains. This is especially remarkable as hemodialysis is a highly standardized therapy. © The Author(s) 2011.