Chagas disease caused by the protozoan Trypanosoma cruzi is the leading cause of heart disease in Latin America. After an acute phase that typically includes few symptoms, a chronic cardiac phase occurs for many infected individuals. The progression to chronic heart disease is not fully understood in Guatemala. The objective of this study was to determine the association between T. cruzi infection and progression to Chagas heart disease in Guatemala and determine if the relation is modified according to vector predominance. Using a community-based cross-sectional approach, 813 individuals from two areas of Guatemala were included in the study: 478 (58.8%) from Jalapa and 335 (41.2%) from Chiquimula. Data including serologic evaluation, electrocardiography (ECGs) and demographics were collected to compare the degree of detectable cardiac abnormalities in infected and uninfected individuals. Overall, T. cruzi seroprevalence was 28.8%, 247 (30.4%) presented an abnormal electrocardiography and 79 (9.7%) were diagnosed as Chagas heart disease. Seroreactivity was statistically (p-value<0.05) associated with abnormal ECG, Chagas heart disease, community, age, occupation, time living in the area, knowledge of the vector, ventricular condition defects and ST-T waves changes. The age and sex-adjusted association between a positive seroreactive and abnormal ECG was higher in Jalapa OR=2.0 (CI95% 1.2, 3.1) than in Chiquimula OR=1.2 (CI95% 0.9, 1.8). These results show the high Chagas-cardiac burden in this population and support the idea that the vector predominance plays an importance role in the association and that this should be taken into account in the design of intervention for vector control.