Objectives To construct profiles of self-reported health indicators to examine differences and similarities between people with lower limb loss and a normative sample (hereafter called the norm) and to compare health indicators between subgroups based on level and etiology of limb loss. Design Survey. Setting General community. Participants Adults with unilateral lower limb loss (N=1091) participated in this study. Eligibility criteria included lower limb loss due to trauma or dysvascular complications and regular use of a prosthesis. Interventions Not applicable. Main Outcome Measures The Patient-Reported Outcomes Measurement Information System 29-item Health Profile version 1.0 measures physical function, pain interference, fatigue, sleep disturbance, anxiety, depression, and satisfaction with participation in social roles. The norm includes 5239 individuals representative of the U.S. general population in sex, age, race, ethnicity, and education. Results People with lower limb loss reported statistically significantly worse physical function, pain interference, and satisfaction with participation in social roles and significantly less fatigue than did the norm. People with transfemoral (ie, above-knee) amputation significantly differed in physical function from people with transtibial (ie, below-knee) amputation. Similarly, people with amputation due to trauma and dysvascular etiology significantly differed in physical function and satisfaction with social roles after adjusting for relevant clinical characteristics. Conclusions People with lower limb loss generally report worse physical function, pain interference, and satisfaction with social roles than do the norm. People with dysvascular amputation reported worse physical function and satisfaction with social roles than did people with traumatic amputation. Health indicator profiles are an efficient way of providing clinically meaningful information about numerous aspects of self-reported health in people with lower limb loss.