Peripheral neuropathy and erectile dysfunction are common conditions that have both been linked to cardiovascular disease and its risk factors, especially diabetes. The aim of this study was to assess the association of large-fiber peripheral neuropathy with erectile dysfunction in adult US males with and without diabetes. We included all men aged ≥40 years from the 2001-2002 National Health and Nutrition Examination Survey (NHANES) with data on erectile dysfunction and peripheral neuropathy (n = 1213, including 206 men with diabetes). Erectile dysfunction was assessed by a single question during a self-paced, computer-assisted self-interview. Peripheral neuropathy was evaluated using standardized 10-g monofilament testing, which assesses lower extremity sensation. We used logistic regression to examine the association of peripheral neuropathy with erectile dysfunction overall and stratified by diabetes status, adjusting for demographic and cardiovascular risk factors. The prevalence of peripheral neuropathy was 26.1% (51.2% in men with diabetes and 22.5% in men without diabetes). There was a significant independent association of peripheral neuropathy with erectile dysfunction overall (odds ratio OR 1.71, 95% confidence interval CI, 1.20-2.43) and among US adult men without diabetes (OR 1.68; 95% CI, 1.11-2.56). The association in adults with diabetes was not statistically significant (OR 1.29; 95% CI, 0.39-4.26), possibly owing to limited power in this subgroup. Our study suggests that decreased lower extremity sensation, even in the absence of diabetes, is common and a novel risk factor for erectile dysfunction.