This study identified clinical (e.g., etiology) and demographic factors related to prosthesis use in persons with upper- and lower-limb amputation (ULA and LLA, respectively) and the effect of phantom limb pain (PLP) and residual limb pain (RLP) on prosthesis use. A total of 752 respondents with LLA and 107 respondents with ULA completed surveys. Factors related to greater use (hours per day) for persons with LLA included younger age, full- or part-time employment, marriage, a distal amputation, an amputation of traumatic etiology, and an absence of PLP. Less use was associated with reports that prosthesis use worsened RLP, and greater prosthesis use was associated with reports that prosthesis use did not affect PLP. Having a proximal amputation and reporting lower average PLP were related to greater use in hours per day for persons with an ULA, while having a distal amputation and being married were associated with greater use in days per month. Finally, participants with LLA were significantly more likely to wear a prosthesis than those with ULA. These results underscore the importance of examining factors related to prosthesis use and the differential effect that these variables may have when the etiology and location of amputation are considered.