Approximately 27-37% of the general population experience prolonged sleep duration and 12-16% report shortened sleep duration. However, prolonged or shortened sleep duration may be associated with serious health problems. A comprehensive, flexible, non-linear meta-regression with restricted cubic spline (RCS) was used to investigate the dose-response relationship between sleep duration and all-cause mortality in adults. Medline (Ovid), Embase, EBSCOhost-PsycINFO, and EBSCOhost-CINAHL Plus databases, reference lists of relevant review articles, and included studies were searched up to Nov. 29, 2015. Prospective cohort studies investigating the association between sleep duration and all-cause mortality in adults with at least three categories of sleep duration were eligible for inclusion. We eventually included in our study 40 cohort studies enrolling 2,200,425 participants with 271,507 deaths. A J-shaped association between sleep duration and all-cause mortality was present: compared with 7 h of sleep (reference for 24-h sleep duration), both shortened and prolonged sleep durations were associated with increased risk of all-cause mortality (4 h: relative risk [RR] = 1.05; 95% confidence interval [CI] = 1.02-1.07; 5 h: RR = 1.06; 95% CI = 1.03-1.09; 6 h: RR = 1.04; 95% CI = 1.03-1.06; 8 h: RR = 1.03; 95% CI = 1.02-1.05; 9 h: RR = 1.13; 95% CI = 1.10-1.16; 10 h: RR = 1.25; 95% CI = 1.22-1.28; 11 h: RR = 1.38; 95% CI = 1.33-1.44; n = 29; P < 0.01 for non-linear test). With regard to the night-sleep duration, prolonged night-sleep duration was associated with increased all-cause mortality (8 h: RR = 1.01; 95% CI = 0.99-1.02; 9 h: RR = 1.08; 95% CI = 1.05-1.11; 10 h: RR = 1.24; 95% CI = 1.21-1.28; n = 13; P < 0.01 for non-linear test). Subgroup analysis showed females with short sleep duration a day (<7 h) were at high risk of all-cause mortality (4 h: RR = 1.07; 95% CI = 1.02-1.13; 5 h: RR = 1.08; 95% CI = 1.03-1.14; 6 h: RR = 1.05; 95% CI = 1.02-1.09), but males were not (4 h: RR = 1.01; 95% CI = 0.96-1.06; 5 h: RR = 1.02; 95% CI = 0.97-1.08; 6 h: RR = 1.02; 95% CI = 0.98-1.06). The current evidence suggests that insufficient or prolonged sleep may increase all-cause mortality. Women may be more susceptible to short sleep duration on all-cause mortality. Copyright © 2016 Elsevier Ltd. All rights reserved.