The mortality associated with hemodialysis (HD) remains high. Recent studies have found that a session time of 4 to 4.5 hours and an ultrafiltration rate of less than 10 cc/h/kg were each independently associated with a decreased mortality among HD patients. We started a thrice-weekly nocturnal HD program in May 2005 and have since enrolled a total of 16 patients. The Kt/V urea (2.6 +/- 0.65 vs. 1.2 +/- 0.16, mean +/- SD, P < .05) and serum phosphorus (4.4 +/- 1.1 v 5.3 +/-1.3 mg/dL, P =.049) values obtained 6 months after enrollment in the nocturnal HD program were significantly better than the baseline values obtained before the initiation of the nocturnal HD program. The ultrafiltration rate was 5.9 +/- 1.7 mL/h/kg 6 months after patients participated in the nocturnal HD program, whereas the rates for these same patients at baseline was 10.3 +/- 4.5 mL/h/kg. Psychosocial assessments were performed at baseline and again at 6 months. No difference was seen in the results of these assessments. We conclude that patients receiving long, in-center thrice-weekly nocturnal HD have a decrease in serum phosphate, an improvement in urea clearance, and a reduction in ultrafiltration rate to less than 10 mL/h/kg. This therapy appears to have no negative impacts on a variety of quality of life measures.