Hypercoagulability could be intrinsic or caused by the hormone treatment preceding the IVF procedure. Endothelial cell protein C receptor (EPCR) enhances the generation of activated protein C by the thrombin–thrombomodulin complex. Soluble EPCR plays a role in the maintenance of pregnancy evidenced by the findings that EPCR expression is critical for embryo development. Specific gene variants linked with altered soluble EPCR levels were associated with poor pregnancy outcome. The aim of this study was to assess the predictive value of EPCR gene polymorphisms (6936A/G, 1651C/G, and 4678C/G) and sEPCR level on the IVF outcome in Egyptian women with repeated IVF failure. They were compared to healthy control patients eligible for IVF. The present study was conducted on 45 women with repeated IVF failure, three or more previous IVF-embryo transfer cycles, and 45 healthy age-matched women eligible for IVF. PCR-RFLP for the EPCR polymorphisms (6936A/G, 1651C/G, 4678G/C) was done for cases and control groups. Plasma-soluble EPCR levels were measured with ELISA. As regards the mutant, EPCR (6936A/G) genotypes (AG, GG) were higher than the wild type (AA) (P < 0.001, OR 4.125, 95% CI 2.198–7.740). The homozygous mutant genotype (GG) was higher in comparison to the wild type (AA). The mutant allele (G) was higher than the wild allele (A) (P < 0.001, or 2.549, 95% CI 1.601–4.061). Higher frequencies of the (1651C/G) genotype and lower soluble EPCR levels were noted both in (C/C) (P = 0.004; Z = −0.2867) and (C/G) (P = 0.006; Z = −0.2767) genotype carriers. Regarding, EPCR polymorphism (4678G/C), the homozygous mutant genotype (CC) was significantly lower than the homozygous wild type (GG), (P = 0.014, OR 0.289, 95% CI 0.108–0.776). Our data suggest that the 6936A/G and 1651C/G EPCR gene variants coupled with procoagulant diminished levels of sEPCR may be associated with a higher tendency for repeated implantation failure.