Background: The association between kidney function and cognitive impairment has not been assessed in a national sample with a wide spectrum of kidney disease severity. Study Design: Cross-sectional. Setting & Participants: 23,405 participants (mean age, 64.9 ± 9.6 years) with baseline measurements of creatinine and cognitive function participating in the REasons for Geographic And Racial Differences in Stroke (REGARDS) Study, a study of stroke risk factors in a large national sample. Predictor: Estimated glomerular filtration rate (eGFR). Outcome: Cognitive impairment. Measurements: Chronic kidney disease (CKD) was defined as eGFR less than 60 mL/min/1.73 m2. Kidney function was analyzed in 10-mL/min/1.73 m2 increments in those with CKD, and in exploratory analyses, across the range of kidney function. Cognitive function was assessed using the 6-Item Screener, and participants with a score of 4 or less were considered to have cognitive impairment. Results: CKD was associated with an increased prevalence of cognitive impairment independent of confounding factors (odds ratio, 1.23; 95% confidence interval, 1.06 to 1.43). In patients with CKD, each 10-mL/min/1.73 m2 decrease in eGFR less than 60 mL/min/1.73 m2 was associated with an 11% increased prevalence of impairment (odds ratio, 1.11; 95% confidence interval, 1.04 to 1.19). Exploratory analyses showed a nonlinear association between eGFR and prevalence of cognitive impairment, with a significant increased prevalence of impairment in those with eGFR less than 50 and 100 mL/min/1.73 m2 or greater. Limitations: Longitudinal measures of cognitive function were not available. Conclusions: In US adults, lower levels of kidney function are associated with an increased prevalence of cognitive impairment. The prevalence of impairment appears to increase early in the course of kidney disease; therefore, screening for impairment should be considered in all adults with CKD. © 2008 National Kidney Foundation, Inc.