BACKGROUND Since the inception of clinical VCA almost two decades ago, burn victims have been identified as immunologically complex patients owing to preformed HLA antibodies. However, it remains unclear whether the detected HLA antibodies are the result of former alloantigenic events or if their de novo formation occurs during primary burn care. METHODS Patients with burns >20% of total body surface area (TBSA) admitted to Zurich Burn Centre between May 2015 and September 2016 were screened for HLA antibodies at admission and 6 months post trauma. The influence of glycerol-preserved donor skin and red blood cell transfusion on HLA antibody formation was investigated. RESULTS Thirty-seven patients (7 females and 30 males) with an average age of 45.2±19.1 years and average affected TBSA of 38.5%±18.9% were screened for HLA antibodies. Five patients (13.5%) showed preformed HLA antibodies at admission. Only 3 patients demonstrated verified de novo sensitization during acute burn care. Six patients treated with donor skin and blood transfusions showed no occurrence of HLA antibodies after 6 months. One patient died after 2 weeks due to infectious and thromboembolic complications - however, HLA antibodies were already detected. CONCLUSION Formation of HLA antibodies during acute burn care might be lower than that previously expected by using glycerol-preserved donor skin and restrictive administration of blood products. Modern concepts of burn care may contribute to a revised outlook on burn patients as potential candidates for VCA.