Summary In this study, we investigated the association between single‐nucleotide polymorphisms (SNPs) of the interleukin‐4 (IL4), interleukin‐4 receptor‐α (IL4RA) and interleukin‐10 (IL10) genes with the development of chagasic heart disease. This study included 260 patients from Colombia who were serologically positive for Trypanosoma cruzi antigens (cardiomyopathic, n = 130; asymptomatic, n = 130). Genotypes were determined by polymerase chain reaction (PCR)–restriction fragment length polymorphism or sequence‐specific primer methods. We found statistically significant differences in the distribution of the IL4RA +148 AA (P = 0·025, OR = 1·89, CI = 1·04–3·43) genotype when comparing asymptomatic and symptomatic patients. No statistically significant differences in the genotype and allele frequency of IL4 and IL10 gene polymorphisms between symptomatic and asymptomatic patients were observed. Our experimental evidence suggests that the IL4RA +148 AA genotype has a weak association with the development of chagasic cardiomyopathy in the population under study.