The study estimates the association of VEGF gene polymorphism (-1154 G/A, -2549 I/D, -2578 C/A, and +936 C/T) in recurrent pregnancy loss from South Indian population. A total of 100 couples with the history of recurrent pregnancy loss and 100 couples with medically terminated pregnancies were considered. Fetal tissues with < 20weeks of gestation including peripheral blood from case and control couples were collected. VEGF gene polymorphisms were determined by allele-specific polymerase chain reaction. Genotypic distribution and allele frequencies were evaluated by odds ratio with 95% confidence intervals. Haplotype analysis was done to determine the association of specific haplotypes with recurrent pregnancy loss. The VEGF -1154 G/A polymorphism was significantly prevalent in the aborted fetuses and in their mothers whereas -2549 I/D polymorphism was significantly higher in the aborted fetuses while the + 936 C/T polymorphism showed prevalence in the case mothers revealing their statistically significant association to recurrent pregnancy loss. A1154D2549A2578T936 haplotype showed an increased risk in case fetuses and mothers whereas A1154D2549C2578C936, in case mothers and fathers while haplotype G1154I2549A2578C936 found a protective association in the case fetuses compared to controls. This is the first report of family-based triad study revealing a significant association of VEGF gene polymorphism in the etiology of recurrent pregnancy loss.