We report a case of one patient who underwent emergency retransplantation with a highly positive donor crossmatch. Standard immunosuppression was integrated by the addition of plasma exchange during extracorporeal circulation, polyclonal IgG, and cyclophosphamide for the first 30 days. After transplantation the clinical outcome was normal; immunosuppression induced a complete disappearance of the donor-specific antibody. In spite of the heavy immunosuppression, we did not observe any infectious complications. We suggest that a greater immunosuppression established soon after the transplant and adjusted on the basis of immunological monitoring may allow a heart transplant with a positive crossmatch.