Recurrent pregnancy loss (RPL) has many known aetiologies. However, using current diagnostic testing, a large fraction of recurrent pregnancy losses remain unexplained. Many of these may have immune underpinnings. HLA-G is a non-classical MHC class I product whose fairly restricted expression at the maternal-fetal interface suggests a role in successful embryonic implantation and/or subsequent pregnancy maintenance. The study of immune-mediated RPL should be enhanced by comparing groups of idiopathic RPL patients with normal fetal chromosomes to RPL patients with known chromosomal abnormalities in their index pregnancies. We hypothesized that if alteration of HLA-G expression at the maternal-fetal interface were associated with immune-mediated RPL, such changes might be detectable using these comparisons. HLA-G protein expression at the maternal-fetal interface in maternal and gestational age-matched women with history of idiopathic RPL and normal male fetuses were compared with expression in RPL patients with known fetal trisomy 16 in their index pregnancy. We detected no significant quantitative differences in the levels of HLA-G between these groups of RPL patients. Within the limitations of this study, we conclude that HLA-G expression is not a major immunological determinant of pregnancy maintenance among patients with idiopathic RPL.