Background: Previous studies indicated an association between endothelial nitric oxide synthase (eNOS) activity and maintenance of pregnancy, but it is rather controversial whether polymorphisms of the gene encoding for eNOS are associated with recurrent spontaneous abortions (RSAs). Aim: The aim was to investigate whether the presence of maternal polymorphism Glu298Asp in exon seven of the eNOS gene increase the risk of RSA in Egyptian women. Subjects and Methods: Hundreds women were randomly selected as the case group. They had at least three RSA before 20th weeks of gestation, same partner and at least one live birth and compared with 100 women, same age range, with no history of abortions or complicated pregnancy as control group. All were investigated for the polymorphism using the polymerase chain reaction‑restriction fragment length polymorphisms method. Data were expressed descriptively as percentages for qualitative values and mean ± standard deviation for quantitative parametric data and comparison of qualitative data was done. Results: Frequency of GG genotype 50/100% in cases and 67/100% in control group. Heterozygous GT frequency was 46/100% in cases and 26/100% in control (P ≤ 0.01, odds ratio [OR] =2.37, and 95% confidence interval [CI] =1.30–4.34). Homozygous TT was 4/100% in the cases and at 7/100% in control (P = 0.68, OR = 0.77, and 95% CI = 0.21–2.76). GG genotype versus GT and GG (P = 0.01, OR = 2.03, and 95% CI = 1.15–3.60). Cases with TT genotype were more susceptible to abortion at an older age with a mean of 29 (4.76) (P = 0.02). Conclusion: In conclusion, (eNOS) Glu298Asp polymorphism was found to be associated with increased risk of RSA in this sample of Egyptian women.