OBJECTIVE 25-hydroxyvitamin D (25[OH]D) deficiency and cognitive impairment are both prevalent in hemodialysis patients in the United States. This study tested the hypothesis that 25(OH)D deficiency may be associated with cognitive impairment because of its vasculoprotective, neuroprotective, and immune-modulatory properties. METHODS This cross-sectional analysis involved 255 patients enrolled in the Dialysis and Cognition Study between 2004 and 2012. In linear regression models, 25(OH)D was the exposure variable; it was used first as a continuous variable and then stratified as deficient (<12 ng/ml), insufficient (12 to <20 ng/ml), and sufficient (≥20 ng/ml). Principal component analysis was used to obtain the memory and the executive function domains from the individual neurocognitive tests. Scores on individual tests as well as on the memory and executive function domains were the outcome variables. Multivariable models were adjusted for age, sex, race, education, and other potential confounding variables. RESULTS Mean serum 25(OH)D ± SD was 17.2±7.4 ng/ml, with 14%, 55%, and 31% of patients in the deficient, insufficient, and sufficient groups, respectively. Patients in the deficient group were more likely to be women, African American, and diabetic and to have longer dialysis vintage. Higher 25(OH)D levels were independently associated with better performance on several tests of executive function (mean difference on component executive score, 0.16 [95% confidence interval, 0.04-0.28; P=0.01] for each SD higher 25[OH]D). No association was seen with tests assessing memory. CONCLUSIONS 25(OH)D deficiency in hemodialysis patients is associated with worse cognitive function, particularly in domains that assess executive function.