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Background: Although endothelial cell protein C receptor (EPCR) gene Ser219Gly polymorphism has been associated with venous thromboembolism (VTE) susceptibility, no clear consensus has yet been reached. Objective and methods: A meta-analysis of 9,494 subjects from 13 individual studies was conducted to better elucidate the potential relationship between the EPCR gene Ser219Gly polymorphism and VTE. Pooled odds ratios (ORs) and their corresponding 95% confidence intervals (CIs) were evaluated by using fixed or random effect models. Results: The current meta-analysis suggested that there was a significant association between EPCR gene Ser219Gly polymorphism and VTE under allelic (OR: 1.42, 95% CI: 1.21–1.66, P = 1.30 × 10−5), recessive (OR: 2.02, 95% CI: 1.44–2.85, P = 5.35 × 10−5), homozygous (OR: 2.24, 95% CI: 1.59–3.16, P = 3.66 × 10−6), and additive genetic models (OR: 1.63, 95% CI: 1.30–2.04, P = 2.24 × 10−5). Conclusions: EPCR gene Ser219Gly polymorphism was associated with an elevated risk of VTE and the Gly residue carriers of the EPCR gene might be predisposed to VTE.