Background: Embryo implantation is a very intricate process, which is controlled by a number of complex molecules like hormones, cytokines, growth factors and their cross talk at feto-maternal interface. The transcription factor nuclear factor kappa B (NF-κB) induces the expression of various pro-inflammatory genes, including those encoding cytokines and chemokines, and also participates in inflammasome regulation. Aim of the present study:was to investigate the possible associations between NF-κB rs28362491 single nucleotide gene polymorphism and susceptibility to repeated implantation failure (RIF). Subjects and Methods: This study was conducted on 120 subjects subdivided into 2 groups: 60 women with successful implantation asacontrol group (Group I), and 60 womendiagnosed withRIF(Group II). They were subjected to full history taking, clinical examination and investigated for molecular testing of the NF-κB -94 ins/del ATTG (rs28362491) polymorphism by lymphocyte separation and extraction of DNA for polymerase chain reaction (PCR) together with determination of serum concentration of  day 3 follicle stimulating hormone (FSH), luteinizing hormone (LH), estradiol II (E2), prolactin and thyroid stimulating hormone (TSH) concentrations by an automated quantitative enzyme-linked fluorescent immunoassay (ELFA). Results: A significant difference in the genotype distribution of the NF-κB rs28362491 between those with RIF and controls. Specifically, subjects with RIF had a significantly higher frequency of the NF-κB rs28362491 del allele than that of controls. Conclusion: This study showed a significant association between rs28362491 in the promoter region of the NF-κB gene and RIF. NF-κB appears to be a triggering factor of orchestrated gene regulation during embryo implantation.