Vascular endothelial growth factor (VEGF) plays an important role in bone health. We investigated the factors which influence circulating VEGF and their association with bone mineral density (BMD). Two hundred and fifty two post-menopausal women aged 64.5 [9.2] years were studied. BMD was determined at the lumbar spine (LS), femoral neck (FN) and total hip (TH). Serum oestradiol and VEGF were measured. Subjects were genotyped for two polymorphic variants in the 5' untranslated region of the VEGF gene; G(634)C and C(936)T. Positive correlations were seen between circulating VEGF and BMI (r=0.2, p<0.02) and oestradiol (r=0.25, p<0.001). Following multi-linear regression analysis, serum VEGF was associated with the G(634) polymorphism (p=0.08) and dietary calcium intake (p=0.02). The association with calcium intake may be mediated by PTH as suggested by the in vitro studies. Following correction for confounders, there was no association between circulating VEGF and BMD at any site. Both VEGF polymorphisms were significant predictors of LS BMD G(634)C: p=0.017 and C(936)T: p=0.05. Circulating VEGF may be influenced by genetic, environmental and endocrine factors. Polymorphic variants in the VEGF gene are associated with spine BMD. Further larger studies are needed.