A 67-year-old man with a recent above-knee amputation surgery presented to the emergency department with fever, tachycardia, hypotension, altered mental status, and a necrotic, foul-smelling amputation stump. He was taking warfarin for atrial fibrillation with an initial international normalized ratio of 6.1. Examination revealed skin crepitus suggestive of an anaerobic infection. Because of his progressive hemodynamic instability and coagulopathy, we performed cryoamputation using dry ice in the intensive care unit for resuscitation and correction of his coagulopathy. The following day, he was hemodynamically stable and taken to surgery for guillotine resection of the frozen infected stump. Two days later, the amputation stump was débrided, and a higher above-knee amputation was reconstructed with viable skin and muscle. At 4 months of follow-up, he was undergoing fitting for an above-knee amputation prosthesis. The initial tissue cultures were positive for Enterococcus faecalis, Clostridium ramosum, Staphylococcus aureus, and group C beta streptococci. Although rarely used, cryotherapy can be useful in a setting of severe infection and an unstable patient. In this case, severe coagulopathy and rapidly progressive infection of the stump were critical factors in the selection of cryotherapy. Used properly, the degree of skin and tissue damage can be limited to the site of the infection, preserving enough of the remaining limb to salvage the amputation stump.