Trypanosoma cruzi is the causal agent of Chagas disease. Of the Mexican states, Veracruz is among the most affected by this sickness. However, the actual epidemiologic situation of this disease is not well understood. This study sought to determine the prevalence and risk factors for Chagas disease among Veracruzan blood donors. Blood donors from Centro Estatal de la Transfusion Sanguinea de Veracruz were included. Blood units were serologically scrutinized for T. cruzi antibodies using enzyme-linked immunosorbent assays. To identify risk factors, demographic data were collected from the medical records of positive donors and a representative sample of healthy donors. A total of 87,232 donations were analyzed, and the mean prevalence of T. cruzi was found to be 0.5%. The identified risk factors were living as a couple and in a rural area, having a low level of education, being a farmer, dwelling in a house with earthen or wooden walls and a tile or thatch roof, living with domestic animals, recognition of or exposure to triatomine bugs, and residing in the Huasteca region. An increase of rural-living donors infected with T. cruzi was observed in the past 3 years of the study period. The prevalence to Chagas disease has not decreased in the past decade and the disease appears to be spreading in rural areas of Veracruz. This increases the risk of T. cruzi transfusion-transmitted infection, not only in Veracruz and Mexico, but also in other nonendemic countries that receive immigrants from Veracruz State. © 2014 AABB.