This report describes the prevalence and characteristics of people with a family history of ESRD in a first-degree relative (FH-ESRD). This is a cross-sectional study of individuals in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) cohort, a population-based sample of US residents who are 45 yr and older. FH-ESRD was ascertained at baseline among 12,030 participants of the cohort, and multivariate logistic regression was used to identify characteristics that were independently associated with FH-ESRD. FH-ESRD was reported by 9.5% of participants. Individual characteristics that were independently associated with FH-ESRD included black race (odds ratio [OR] 2.14; 95% confidence interval [CI] 1.82 to 2.53); female gender (OR 1.28; 95% CI 1.08 to 1.51); a history of diabetes (OR 1.22; 95% CI 1.02 to 1.47); a 1-SD change in the log of the C-reactive protein level (OR 1.10; 95% CI 1.01 to 1.19); and World Health Organization body mass index weight categories normal (OR 2.11; 95% CI 0.66 to 6.79), overweight (OR 2.64; 95% CI 0.82 to 8.42), and obese (OR 3.48; 95% CI 1.09 to 11.1) compared with underweight. Black but not white individuals with FH-ESRD were more likely to have an estimated GFR <60 ml/min per 1.73 m2. There is a high prevalence of FH-ESRD among US adults, and the prevalence of FH-ESRD was higher among lack individuals. Individuals with a positive family history were more likely to have diabetes and to be obese. If confirmed, then these findings suggest that individuals with FH-ESRD may benefit from interventions to improve the detection and treatment of chronic kidney disease risk factors such as diabetes and obesity. Copyright © 2007 by the American Society of Nephrology.