ObjectiveRecurrent pregnancy loss is one of the most common medical events that occur in the first and second trimesters. Hence, this study aimed to evaluate the relationship between vitamin D receptor (VDR) polymorphisms (rs2228570 and rs7975232) and the risk of recurrent pregnancy loss. The effect of rs2228570 polymorphism on protein stability was also predicted via in silico investigation. MethodsThis cross-sectional study was conducted on 52 women with recurrent pregnancy loss and 52 control women without pregnancy loss. We used the polymerase chain reaction technique to amplify the polymorphism regions on the chromosome. The PCR products were cut by FokI and ApaI restriction enzymes and the obtained data were analyzed. ResultsOur results showed the case group consisted of 32.7% wild type, 65.4% heterozygote, and 1.9% homozygote genotypes for polymorphism rs7975232.The controls included 48.1% wild type, 42.3% heterozygote, and 9.6% homozygote genotypes. There was a significant difference between polymorphism rs7975232 and recurrent pregnancy loss (P = 0.034). These genotypes for rs2228570 polymorphism were53.8% wild type, 38.5% heterozygote, and 7.7% homozygote. However, the control group included 80.8% wild type, 15.4% heterozygote, and 3.8% homozygote. There was a significant difference between polymorphism rs2228570 and recurrent pregnancy loss (P = 0.014). ConclusionWe found a significant difference between VDR rs2228570 and rs7975232 genetic variants with recurrent pregnancy loss. Protein stability was also decreased following single nucleotide polymorphism in VDR rs2228570.