The non-classical class I human leukocyte antigen (HLA)-G molecule was found to be predominately expressed in the extravillous cytotrophoblasts at the fetal-maternal interface during pregnancy. This molecule is critically important for successful implantation during human pregnancy. The polymorphic insertion-deletion (indel) 14-base pair (bp) site localized at the 3' untranslated region was associated with HLA-G mRNA stability and isoform alternative splicing patterns, and thus may influence HLA-G function during pregnancy. We studied the association between the 14-bp indel polymorphism (rs16375) at the 3' untranslated region with recurrent spontaneous abortions in a Saudi population living in Riyadh. A group of 64 women with 2-11 successive abortions were included in this study. The control group included 62 women without reported abortions and at least 2 pregnancies, all visiting the King Khaled Hospital in Riyadh. The 14-bp indel was genotyped in the case and control groups. The frequency of the genotype +14/+14 was slightly higher in women with recurrent spontaneous abortions, but no significant differences were observed in the distribution of alleles and genotypes.