Background: Endometriosis is a chronic gynecological disease resulting from complex interactions between genetic, hormonal, environmental and oxidative stress and intrinsic inflammatory components. The aim of this study was to investigate the potential association of the 763C>G polymorphism in the secretory phospholipase A2 group IIa gene (PLA2G2A) with the risk of endometriosis in Iranian women.Materials and Methods: Ninety seven patients with endometriosis along with 107 women who were negative for endometriosis after laparoscopy and laparatomy, and served as the control group, were enrolled for this cross-sectional study. Samples were genotyped using the polymerase chain reaction-restriction fragment length polymorphism method.Results: Multivariate analysis was used to examine the association between the risk of endometriosis and the763C>G polymorphism of PLA2G2A. Genotype distributions of PLA-2G2A were significantly different between patients and the controls (p<0.001, OR=0.22, 95% CI=0.21-0.39). Correlation analysis showed that there was a significant association between the normal homozygous genotype and susceptibility to endometriosis (p<0.001).Conclusion: The present study suggests that the 763C>G polymorphism of PLA2G2A plays an important role as an independent factor in the risk of endometriosis in Iranian women.