Venous thromboembolism (VTE) is a common, yet complex disorder. Genetic factors have been suggested to play a role in disease development. We, therefore, conducted a case-control study to examine the potential association of the 6936A/G polymorphism in the endothelial cell protein C receptor (EPCR) gene with the occurrence of venous thromboembolism. We measured the plasma levels of soluble EPCR (sEPCR) in blood samples collected from 112 patients with VTE and 112 age- and gender-matched healthy donors using enzyme-linked immunosorbent assay (ELISA) and amplified the EPCR gene product by PCR. Gene product bands were sequenced to identify EPCR gene polymorphisms. We found that the 6936 AG and GG genotypes were over-represented in the VTE patients. By multivariate analysis, subjects carrying the 6936 G allele were found to have an increased risk of thrombosis (OR=1.784; 95% CI, 1.113-2.891; P<0.05). In conclusion, the EPCR gene 6936A/G polymorphism, which is associated with elevated plasma sEPCR levels, is a potential candidate risk factor for venous thromboembolism.