Introduction Burn center patients present not only with burn injuries but also necrotizing infections, purpura fulminans, frostbite, toxic epidermal necrolysis, chronic wounds, and trauma. Burn surgeons are often faced with the need to amputate when limb salvage is no longer a viable option. The purpose of this study was to determine factors which predispose patients to extremity amputations. Methods: This retrospective registry review (2000-2019) compared patients who required upper extremity amputations with those who did not. Cases were pair-matched by age, sex, percent total body surface area (%TBSA), and type/location of injury to control for possible confounding variables. Results: There were 77 upper extremity amputee patients (APs) and 77 pair-matched non-amputees (NAPs) with the median age 45- and 43-years, %TBSA 21 and 10, respectively; second and third degree burn injuries were similar in the 2 groups. The AP group had longer hospitalizations (median 40 vs 15 days) P < .0001, with more intensive care unit days (median 28 vs 18 days). APs presented with significantly more cardiac, renal, and pulmonary comorbidities, acquired infections (61 [64%] vs 35 [36%]), escharotomies, and fasciotomies than the NAP, P < .0001. Mortality was similar (AP 14 [18.2%] vs NAP 9 [11.7%]), P = .26. Conclusions: Escharotomies, fasciotomies, sepsis, pneumonia, wound, and urinary tract infections contributed to prolonged hospitalizations and increased risk for upper extremity amputations in the AP group.