Abstract: Osteoporosis is a condition characterized by low bone mineral density (BMD) and micro-architectural changes in the bone tissue. The risk of osteoporosis is partly determined by genetic factors. The role of C677T polymor-phism of methylenetetrahydrofolate reductase (MTHFR) gene has been investigated in postmenopausal oste-oporosis. However, the relationship between MTHFR polymorphism and BMD is still controversial. We carried out a meta-analysis of 5,833 subjects to evaluate the association of MTHFR and BMD in postmenopausal women. Databases of MEDLINE, Web of Science, Scopus and CNKI were retrieved for all publications relating to MTH-FR polymorphism and BMD in postmenopausal women. Five eligible studies were selected for meta-analysis. All these articles studied the association of MTHFR polymorphism and BMD of the femoral neck and lumbar spine in postmenopausal women. Our analysis suggested that postmenopausal women with the TT genotype had lower femoral neck BMD than the women with the CC/CT genotype, and the weighted mean difference (WMD) was -0.01 g/cm2 95% confidence interval (CI): (-0.01, -0.01), P < 0.01. However, BMD of the lumbar spine of postmenopausal women with the TT genotype was not significantly different from that of women with the CC/CT genotype. In the random effects model, the WMD between the TT and TC/CC genotype was -0.01 g/cm2 95% CI: (-0.04, 0.01), P = 0.32. The C677T polymorphism of the MTHFR gene is associated with BMD of the femoral neck in postmenopausal women. Women with the TT genotype of the MTHFR gene have lower BMD, suggesting that the TT genotype may be a risk factor for postmenopausal osteoporosis.