Background: Patients treated with conventional hemodialysis have poor physical performance, explained by insufficient metabolic clearance and shortage of time by time-consuming dialysis. Nocturnal hemodialysis improves metabolic control and results in increased spare time. Our aim is to investigate whether physical performance in nocturnal hemodialysis is superior to conventional hemodialysis. Methods: A systematic search was conducted in MEDLINE, Embase, CINAHL, PhycInfo and Web of Science until January 2018. Primary outcomes were physical performance, activity, strength and muscle mass in home or in-center nocturnal hemodialysis. Methodological quality was assessed with the Newcastle-Ottawa scale. Results: Ten studies met the inclusion criteria, including 2 RCTs, evaluating 526 nocturnal hemodialysis patients with a mean follow-up of 15, 3 months. The methodological quality of 4 studies was limited. Physical capacity tests were done in 3 studies with different methodology: short-physical performance battery, exercise spirometry and 6-min walk test. The latter 2 showed significant improvements in physical performance. Four studies assessed lean mass using dual-energy X-ray absorptiometry (2×) and bioelectrical impedance analysis (2×), of which 1 demonstrated increased lean body and skeletal muscle mass. In 5 studies a Quality of Life questionnaire was used, of which 2 showed improved physical component score. Conclusions: The evidence on the effect of nocturnal hemodialysis on physical performance is either of insufficient methodological quality or only measures isolated aspects of physical performance. As literature emphasizes the importance of physical activity on clinical outcomes, it is necessary to conduct larger studies of high methodological quality using capacity tests for answering the question whether nocturnal hemodialysis can improve physical performance of patients with end-stage renal disease. Trial registration: NTR4715, Netherlands Trial Register. Registered 30 July 2014.