The signal transduction pathways mediating the progress of heart failure have been intensively studied. Altered signaling of the signal transducers and activators of transcription (STATs), which play important roles in regulating cell proliferation, differentiation, and apoptosis, has been observed in the heart. We conducted a pilot study to test whether single nucleotide polymorphisms (SNPs) in STATs were associated with dilated cardiomyopathy (DCM). Genotypes of two SNPs of STATs (rs6503691 C/T in exon 1 of STAT5B and rs4796793 C/G in the 5' region of STAT3) in 251 DCM patients and 484 control subjects were determined with the use of PCR-restriction fragment length polymorphism assay and TaqMan assay, respectively. Significantly increased DCM risk was found to be associated with T allele of rs6503691 (P = 0.012, OR = 1.37, 95% CI = 1.07-1.74). We found that increased DCM risk statistically significantly associated with rs6503691 in a dominant model (P = 0.009, OR = 1.50, 95% CI = 1.11-2.04). No association between DCM risk and rs4796793 was observed (P = 0.706, OR = 1.05, 95% CI = 0.83-1.32). The present pilot study provides evidence that both rs6503691 T allele and CT/TT genotypes, but not rs4796793 C/G in the 5' region of STAT3, are associated with a significantly increased risk of DCM, indicating that common genetic polymorphism in STATs is associated with DCM.