A 62-year-old man with a history of ischemic cardiomyopathy underwent orthotopic heart transplantation. Before transplantation, he completed three monthly cycles of plasmapheresis, with administration of IV immunoglobulin (Ig) to reduce the level of preexisting human leukocyte antigen antibodies. On the day of transplant, he was determined to be IgG seropositive for cytomegalovirus and Toxoplasma gondii. The patient was induced with alemtuzumab and received tacrolimus and mycophenolate mofetil for immunosuppression. He recovered uneventfully in the early posttransplant course.