Donor infection status should be considered when accepting an organ for transplant. Here we present a case of Chagas disease developing after a lung transplant where the donor was known to be Trypanosoma cruzi antibody positive. The recipient developed acute Trypanosoma cruzi infection with reactivation after treatment. Chagas disease-positive donors are likely to be encountered in the United States; donor targeted screening is needed to guide decisions regarding organ transplant and posttransplant monitoring.