<i>Background/Aims:</i> Patients value health-related quality of life (HRQOL) over survival. It was our aim to study the relation between attainment of widely accepted performance targets and HRQOL in hemodialysis patients. <i>Methods:</i> This study included baseline data from 715 hemodialysis patients from 29 dialysis centers. Six clinical performance targets, as recommended by the Kidney Disease Outcomes Quality Initiative (KDOQI), were evaluated: single-pool Kt/V (≧1.2), hemoglobin (11–13 g/dl), vascular access (fistula), phosphorus (2.3–4.5 mg/dl), parathyroid hormone (150–300 pg/ml), and blood pressure (predialysis <140/90 and postdialysis <130/ 80 mm Hg). <i>Results:</i> After correction for case-mix and multiple comparisons, no association was found between the 6 KDOQI clinical performance targets and the 14 HRQOL domains, or between the number of performance targets reached and HRQOL. <i>Conclusion:</i> Attainment with widely accepted clinical performance targets was not related to the HRQOL of hemodialysis patients. Hence, in clinical guidelines, HRQOL should be adopted as an explicit treatment goal for these individuals.