The purpose of this study was to investigate the association of the g.27667T>A genetic variant in the osteoprotegerin (OPG) gene with bone mineral density (BMD) and osteoporosis. A total of 393 primary osteoporosis subjects and 402 healthy controls were recruited. The BMD of the femoral neck hip, lumbar spine (L2-4), and total hip were evaluated by Norland XR-46 dual-energy X-ray absorptiometry. The g.27667T>A genetic variant was genotyped using created restriction site-polymerase chain reaction. Our data indicated significant differences in BMD of the femoral neck hip, lumbar spine (L2-4), and total hip among different genotypes. Individuals with the genotype TT had significantly higher BMDs than those of genotypes TA and AA (P<0.05). Results from this study suggest that the g.27667T>A genetic variant in the OPG gene is potentially related to BMD and osteoporosis in Chinese postmenopausal women.