PURPOSE: Calcium signaling is essential for immune function, myometrial contractions, and hormone secretion, all of which contribute to preterm birth. In this study, we investigated the associations of 3 single-nucleotide polymorphisms (SNPs) in CACNA1D gene, which encodes the Cav1.3 calcium channel, with the risk of spontaneous preterm birth (sPTB). METHODS: A hospital-based case-control study was conducted with 112 women of sPTB and 1120 term control women. Three CACNA1D SNPs (rs9810888 T/G, rs1045958 C/T, and rs881883 G/A) were genotyped. RESULTS: The T/G genotype of the CACNA1D rs9810888 SNP was associated with a reduced risk of sPTB (odds ratio: 0.61, 95 % confidence interval: 0.41-0.91, P = 0.01, P CONCLUSION: Our findings suggest that the intronic rs9810888 T/G variant of CACNA1D gene protects against sPTB in Taiwanese women.