We examined 179 patients with and without preterm rupture of fetal membranes. The mothers and their newborns have been genotyped by two polymorphic loci of estrogen receptor α (ESR1) gene: -397T > C[PvuII] (rs2234693) and -351A > G[XbaI] (rs9340799). The CG haplotype of the fetus should be regarded as a risk factor of preterm rupture of fetal membranes, while haplotype TA as a protective factor. Genotype -351A/A is a marker of the protective haplotype in the fetus, while genotype -397C/C is a marker of the risk haplotype, which can be used in combined analysis of both markers. These data attest to an important role of fetal genotype in the formation of genetic predisposition to preterm rupture of fetal membranes.