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Skin allografts are the gold standard in temporary burn wound coverage, but allografts are hypothesized to place a high antigenic load on recipients. This project aims to determine the degree of human leukocyte antigen sensitization in burn patients treated with allografts. Serum was obtained from nine adult, nontransfused, and nontransplanted burn patients treated with allografts. Group 1 included patients tested in the acute burn period, while group 2 included different patients tested months to years after injury. A calculated panel reactive antibody (cPRA) percent was assessed for each patient, and data for a control group of 92 adult nontransplanted males were used for comparison. Each patient received allografts from an average 3.55 ± 1.24 different donors. cPRA in group 1 was lower than in group 2 (6 ± 12% vs 42 ± 33%, P = .08). cPRA in the study group was significantly higher than in the control group (26 ± 31% vs 8 ± 17%, P = .0075). Burn patients who receive skin allograft demonstrate increased immunological sensitization compared with unsensitized controls. Detection of human leukocyte antigen antibody is lower in the acute burn period than months to years after injury. Increased sensitization may ultimately limit burn patients’ candidacy for vascularized composite allotransplantation or decrease success of these procedures.