© 2018 American Congress of Rehabilitation Medicine 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.