<p>Background: Recurrent Spontaneous Abortion (RSA) is caused by multiple genetic and non-genetic factors. Around 50% of the RSA cases have no known etiology and are considered as Unexplained RSA (URSA). Estrogens, <em>via</em> binding to their receptors, play an important role in female reproduction. This study aimed to investigate whether single nucleotide polymorphisms (SNPs; +1082G/A, +1730G/A and rs1256030C/T) in the estrogen receptor beta (<em>ESR2</em>) gene are associated with susceptibility to URSA in a population of Iranian women.<br /> Methods: In this case-control study, the study groups consisted of 240 subjects with a history of URSA and 102 fertile women as controls. Serum levels of follicle stimulating hormone (FSH), luteinizing hormone (LH), and estradiol (E2) were measured on day 2-3 of menstrual cycle. Two functional SNPs, +1082G/A (a silent mutation in exon 5) and +1730G/A (3&#39; untranslated region of the exon 8),and one intron,rs1256030C/T, in the ESR2 gene were genotyped, using polymerase chain reaction- restriction fragment length polymorphism (PCR-RFLP) analysis.<br /> Results: Serum levels of LH were significantly increased in URSA women. No significant differences in distribution of +1082G/A, +1730G/A and rs1256030C/T between URSA and control groups were observed.<br /> Conclusion: Our findings suggest that the studied SNPs on <em>ESR2</em> gene may not be associated with URSA.</p>