Abstract Chagas disease continues to cause substantial morbidity and mortality in endemic areas in Latin America. Although there have been some well documented successes in halting the transmission of Chagas disease through preventive interventions to decrease vector-borne and blood-transfusion cases, this parasitic infection continues to be transmitted through these routes in some areas as well through perinatal and foodborne routes. In addition, transmission through solid-organ transplantation has been described in nonendemic settings due to the increasing globalization of Chagas disease to the United States of America, Europe, and other areas. Because there has been a concomitant increase in the number of solid-organ transplantations performed in Latin American settings endemic for American trypanosomiasis, there is increasing concern for the potential reactivation of Trypanosoma cruzi in a previously infected recipient and as a result of aggressive immunosuppression; or via transmission from organs donated by a latently infection donor transplanted onto an uninfected recipient. In this study, we report 2 cases of Chagas disease reactivation in 2 solid-organ transplant recipients in Northeastern Colombia, and we discuss the implications for screening as a crucial strategy for preventing transmission in endemic settings.