Two lower-extremity diseases (LEDs), including peripheral neuropathy and peripheral vascular disease (PVD), are leading causes of disability in the U.S. Although LEDs can be complications of diabetes, their prevelances and risk factors apart from diabetes are poorly described. This study describes the prevalence of LEDs and examines the association of obesity and cardiometabolic clustering in a population-based sample. Adults aged >40 years (n = 2,514) were evaluated in the 2001-2004 National Health and Nutrilion Examination Survey for clustering of two or more cardiometabolic characteristics, including elevated triglycerides or plasma glucose, low HDL cholesterol levels, increased waist circumference, or hypertension. Clustering was combined with BMI (dichotomized at e30 kg/m^sup 2^) to generate three groups: obese (with or without clustering); nonobese with clustering; and nonobese without clustering. Multivariate logistic regression procedures incorporated the complex survey sampling design. Overall, 9.0% of individuals had peripheral neuropathy alone, 8.5% had PVD alone, and 2.4% had both LEDs. The obese group was more likely to have peripheral neuropathy (odds ratio 2.20 [95% CI 1.43-3.39]), PVD (3.10 (1.84-5.22]), and both LEDs (6.91 [2.6418.06]) compared with nonobese subjects without clustering. Within the nonobese group, clustering increased the odds of peripheral neuropathy (1.50 [1.00-2.25]) and PVD (2.48 [1.38-4.44]) compared with no clustering. Obesity and clustering markedly increased the likelihood of LEDs in this sample and identified a group for whom preventive activities may reduce the risk of future disability.