Approximately 75% of major lower-extremity amputations are the result of peripheral vascular disease (PVD). Factors that predispose a patient to PVD (smoking, hyperlipidemia, diabetes mellitus) are also risk factors for the development of cerebrovascular disease, which could adversely affect rehabilitation. The purpose of this study was to test the hypothesis that cognitive deficits are present in amputee patients with PVD. Fourteen patients with lower-extremity amputations secondary to PVD (4 women, 10 men; mean age = 67.4 years) were recruited from a tertiary-care center for physical rehabilitation. Fourteen community-dwelling healthy volunteers (9 women, 5 men; mean age = 69.9 years) served as age-matched and education-matched controls. To assess a broad range of cognitive function, we administered standard neuropsychological tests of memory and learning, language, praxis, visuospatial skills, and abstract reasoning. PVD patients performed significantly more poorly on certain measures of psychomotor speed (Wechsler Adult Intelligence Scale-Revised Digit Symbol subtest) and problem solving/abstract reasoning (Modified Card Sorting Test) relative to controls (using the Bonferroni correction for multiple comparisons, p < .002). There were trends toward poorer patient performance on certain measures of oral fluency, concentration, reasoning, and visuoperceptual organization and constructional skills (p < .01). We propose that these cognitive deficits may be the result of unrecognized concomitant cerebrovascular disease in PVD patients and are part of a generalized pattern of vascular disease. Future research should control affective factors such as stress or depression surrounding amputation and attempt to identify the etiologic or demographic factors that are associated with neuropsychological deficits in patients with PVD.