Cardiovascular disease is the principal cause of death in end-stage renal disease (ESRD) patients. Endothelial progenitor cells (EPCs) play a critical role in vascular repair, and improving EPC biology represents a novel therapeutic target. Three groups of age- and gender-matched patients were studied: 1) 10 healthy control, 2) 12 conventional hemodialysis (CHD) patients, and 3) 10 nocturnal hemodialysis (NHD) patients. EPC number and migratory function were assessed. Left ventricular mass index (LVMI) was derived, and correlations between EPC biology, uremic clearance, and LVMI were made. Compared with controls, EPC number and function were markedly impaired in CHD patients [(3.48 +/- 1.2 vs. 0.86 +/- 0.20%/50,000 cells, P < 0.05) and (18.8 +/- 2.64 vs. 3.75 +/- 0.34 cells/high-power field, P < 0.05), respectively]. In contrast, EPC number and function were normal in NHD patients [(3.48 +/- 1.17 vs. 3.83 +/- 0.77%/50,000 cells) and (18.8 +/- 2.6 vs. 22.2 +/- 2.4 cells/high-power field), respectively]. Among ESRD patients, EPC number and function inversely correlated with predialysis urea concentration (r = -0.40; r = -0.57), LVMI (r = -0.41; -0.46) and systolic BP (r = -0.58; r = -0.44). We demonstrate that NHD is associated with restoration of abnormal EPC biology in ESRD. Given the increasing importance of EPCs in the repair and restoration of cardiovascular function, these data have important clinical implications for vascular risk in ESRD patients.