The aim of this study was to investigate the role of the IL-6-174G/C gene polymorphism in susceptibility/resistance to Trypanosoma cruzi infection in two independent cohorts from Colombia and Peru. We determined the IL-6-174G/C genotypes in a sample of 399 seronegative individuals and 317 serologically positive patients from Colombia and Peru. All individuals are from regions where T. cruzi infection is endemic. No statistically significant differences in the frequency of IL-6-174G/C gene polymorphism between chagasic patients and controls or between asymptomatic and individuals with cardiomyopathy were observed. Our results do not support an evidence for a major role contribution of this IL-6 gene polymorphism in the susceptibility to or clinical manifestations of Chagas disease in these studied cohorts.