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Lung transplant candidates who are highly sensitized against human leucocyte antigen have a lower likelihood of graft allocation and a higher risk of dying while on the waiting list. C1-esterase inhibitor, an inhibitor of the classical and lectin pathways of complement activation, has been used successfully to prevent and treat acute antibody-mediated rejection in kidney and heart transplantation. Here, we report 3 cases of C1-esterase inhibitors used perioperatively in highly sensitized lung transplant candidates, with successful bilateral lung transplants despite severe primary graft dysfunction and/or hyperacute antibody-mediated rejection.