Objective: To explore the association between the genetic variant of E-cadherin gene and endometriosis-related infertility. Design: Case-control study. Setting: University hospital. Patient(s): Five hundred eighty-nine women with ovarian endometriosis including 127 patients with primary infertility and 589 female controls in northern China. Intervention(s): None. Main Outcome Measure(s): Single nucleotide polymorphisms (SNPs) in the promoter region, exons, and the 30 untranslated region of the E-cadherin gene were identified by direct sequencing in patients with ovarian endometriosis and with polymerase chain reaction (PCR). Six candidate SNPs (rs16260, rs28372783, rs1801552, rs1801026, rs8049282, and rs13689) were genotyped by PCR and ligase detection reaction. Result(s): The results revealed a significant association of rs8049282 SNP on E-cadherin gene with endometriosis-related infertility. When compared with control women or endometriosis patients who had a history of successful fertility, the CC genotype of rs8049282 may significantly increase the risk of primary infertility in patients with ovarian endometriosis (adjusted odds ratio [OR] = 2.70, 95% confidence interval [CI] 1.45-5.00; OR = 2.54, 95% CI 1.45-4.44, respectively). Conclusion(s): Our results suggested that genetic variants on the E-cadherin gene may be involved in endometriosis-related infertility. The rs8049282 SNP of the E-cadherin gene may be a potential molecular marker for the development of primary infertility in northern Chinese women with ovarian endometriosis. (C) 2014 by American Society for Reproductive Medicine.