Objective To establish a comprehensive profile of cognitive functioning in people engaged in lower limb amputation (LLA) rehabilitation. Design Cross-sectional study as part of a longitudinal prospective cohort. Setting A national tertiary rehabilitation hospital. Participants Adult volunteer participants (N=87) referred for comprehensive rehabilitation for major LLA were sampled from 207 consecutive admissions. Participants with both vascular (n=69) and nonvascular (n=18) LLA etiologies were included. Interventions Not applicable. Main Outcome Measures Demographic and health information and a battery of standardized neuropsychological assessments. Results Compared to normative data, impairment was evident in overall cognitive functioning (P≤.003). Impairment was also evident in particular areas, including reasoning, psychomotor function, information processing, attention, memory, language/naming, visuospatial functions, and executive functions (all P≤.003 Holm-corrected). There were also higher frequencies of impaired functions across most aspects of functioning in this group compared with expected frequencies in normative data (P≤.003 Holm-corrected). There were no significant differences in cognitive functioning between participants of vascular and nonvascular LLA etiology. Conclusions Findings support the need for cognitive screening at rehabilitation admission regardless of etiology. Administration of comprehensive neuropsychological assessment with a battery sensitive to vascular cognitive impairment is recommended in some cases to generate an accurate and precise understanding of relative strengths and weaknesses in cognitive functioning. Cognitive functioning is a potential intervention point for improvement of rehabilitation outcomes for those with LLA, and further research is warranted in this area.