Hemodialysis has been associated with reduced quality of life (QOL). Small cohort studies of quotidian hemodialysis regimens suggest general QOL and dialysis-related symptoms may improve compared with conventional regimens. An observational cohort study was conducted on 63 patients (age 51.7 +/- 12.9 years; 79.4% male; 33.3% diabetes; duration of renal replacement therapy 1.9 [0.7-6.4] years) converted from conventional home hemodialysis (3-5 sessions weekly, 3-6 h/session) to home nocturnal home hemodialysis (NHD) (3-5 sessions weekly, 6-10 h/session). Kidney Disease Quality of Life (KDQOL) and Assessment of Quality of Life instruments and 6-minute-walk tests were applied at baseline and 6 months. Baseline and 6 month surveys were returned by 70% of patients. On KDQOL, significant improvements in general health (P=0.02) and overall health ratings (P=0.0008), physical function (P=0.003), physical role (P=0.018), and energy and fatigue (P=0.027) were documented. There was a trend toward improvement in burden of kidney disease (P=0.05) and emotional role (P=0.066). There was a significant improvement in distance covered in the 6-minute-walk test from 513 m (420.5-576.4) to 536.5 m (459-609), P=0.007. On Assessment of Quality of Life, there was a trend toward improvement in overall utility score from 0.65 (0.39-0.81) to 0.73 (0.46-0.86), P=0.096. After 86.2 patient-years of observation, 23 patients have discontinued NHD (12 transplanted, 5 deceased, 4 psychosocial problems, 1 dialysis access problem, 1 medically unsuitable). Nocturnal home hemodialysis is a sustainable therapy. In addition to improving general QOL, alternate nightly NHD can significantly improve physical functioning as measured by KDQOL and 6-minute-walk tests.