ObjectiveTo explore the effect of intracellular water (ICW) evaluated by the bioelectrical Impedance Spectroscopy (BIS) on the risk of incident cognitive impairment (CI) in chronic hemodialysis (HD) patients.MethodsThree thousand three hundred eighty‐five patients were recruited and monitored prospectively for up to 3 years (the median follow‐up time, 2 years) in this observational cohort study. Mini‐Mental State Examination score (MMSE) was used to assess the global cognitive function. ICW was measured by body composition monitor based on BIS. Multiple Cox regression models, stratified analyses, and interactive analyses were conducted.ResultsDuring the follow‐up period, 1256 patients (37.1%) experienced incident CI. The incidence of CI was increased with decreasing quartiles of ICW (27.4%, 32.2%, 38.9%, and 50.1% for the fourth, third, second, and first quartiles, respectively). Decreased ICW was significantly associated with incident CI. The association remained statistically significant even after adjusting for age, sex, education, albumin, C‐reactive protein, residual renal function and various medical histories. The hazard ratios were 1.38 (1.17–1.64) and 1.28 (1.08–1.52) for ICW quartile 1 and quartile 2, respectively (reference, quartile 4). The association stably existed across subgroups, and the residual renal function had an interactive role in the association between ICW and incident CI (p = 0.014).ConclusionLow baseline ICW was an independent risk factor for CI in chronic HD patients. Our finding highlights the necessity of using BIS to measure body composition when assessing the risk of CI in HD patients.