Background Postmenopausal osteoporosis (PMO) is the most common type of primary osteoporosis. ESR1 polymorphism rs2234693 and rs9340799 has been widely studied as a candidate gene associated with PMO, however, the findings were inconclusive. The present study aims to explore the relationship of ESR1 polymorphism rs2234693 and rs9340799 with PMO risk in a Chinese Han population. Methods A total of 230 unrelated PMO patients and 150 control were recruited. DNA of all participants was extracted from the peripheral blood samples and genotyped by Mass Array method. A meta-analysis of case control studies was also conducted to further elucidate the relationship of polymorphism with PMO. Results Our results revealed that there were no associations of the rs2234693 with PMO. However,GG genotype of rs9340799 was associated with a higher risk of PMO (OR=1.51, 95%CI:1.08-4.34, p=0.03), even adjusting for risk factors (OR=1.83, 95%CI: 1.12-5.04, p=0.04). Logistic regression analysis showed the dominant model was associated with a higher risk of PMO (OR = 2.07, 95%CI: 1.02-5.16, p=0.02) after correcting the risk factors (OR=2.14, 95%CI:1.12-5.64, p=0.04); In addition, the Meta-analysis results revealed that both two polymorphisms were not associated with PMO. Conclusion In conclusion,ESR1 polymorphism rs9340799 was associated with PMO, However, well designed study with larger sample sizes, is required to further elucidate these association.