Coma blisters are self-limited cutaneous bullae that occur in the setting of loss of consciousness because of a drug, illness, or accident, with the most common settings being barbiturate overdose and neurological disorders. The etiology behind coma blisters is poorly understood and is not related to underlying infections or autoimmune conditions. The clinical presentation consists of bullae, erosions, and violaceous plaques usually involving sites of pressure. The skin lesions usually occur within 48-72 hours of the start of a coma and resolve within 2-4 weeks. We present one case of a 5-month-old infant with severe valvular disease who required surgical repair. He was placed on extra corporeal membrane oxygenation and developed multiple tense coma blisters during the course of therapy. Skin biopsy revealed a noninflammatory subepidermal blister with necrosis of the overlying epidermis and necrosis of the eccrine ducts. We also present a second case of an 18-year-old female patient who underwent surgical resection of a benign mandibular tumor. She subsequently developed bullae on both arms 4 days after surgery. The skin biopsy showed a necrotic epidermis, a subepidermal blister, and diffuse necrosis of the eccrine coils.