BACKGROUND: The activin A receptor type 2A gene (ACVR2A) plays an important role in normal gestation, particularly in decidualization, trophoblastic invasion, and placentation. Although several studies have investigated the association between ACVR2A maternal variants and preeclampsia (PE) susceptibility; however, controversial results were obtained. Moreover, in none of the previous studies, the role of ACVR2A fetal variants was explored. The aim of the present study was to investigate the role of ACVR2A rs1424954 and rs1424941 polymorphisms in PE susceptibility considering the impact of both fetal and maternal genotypes. METHODS: For genotyping of ACVR2A rs1424954 and rs1424941, we performed TP-ARMS-PCR on 600 samples, including 400 peripheral blood samples from preeclamptic and normal women and 200 umbilical cord blood samples from each group of pregnant women. RESULTS: Regarding rs1424954, only the fetal genotypes were associated with an increased risk of PE in both dominant and recessive inheritance models (OR = 2.88, 95% CI: 1.58-5.25, p = 0.0005; and OR = 2.43, 95% CI: 1.21-4.87, p = 0.012; respectively). For ACVR2A rs1424941variant, both maternal and fetal heterozygote genotypes were associated with PE susceptibility (OR = 1.57, 95% CI: 1.02-2.04, p = 0.04; and OR = 1.90, 95% CI: 1.02-3.54, p = 0.04; respectively). CONCLUSION: The present study confirmed the role of fetal ACVR2A polymorphisms in PE pathogenesis for the first time. However, replicated studies in diverse ethnicities are necessary to confirm the role of fetal genotype on susceptibility to PE.