We investigated the temporal association between placental vascular endothelial growth factor (VEGF), a potent stimulator of angiogenesis and vascular permeability, and changes in placental/endometrial vascularity on selected days throughout gestation in the pig. Placental and endometrial tissues were collected from sows on Days 25 (n = 4), 36 (n =6), 44 (n =6), 70 (n =5), 90 (n =5), and 112 (n =7) of gestation. Cross sections of the placental/endometrial interface of each conceptus were used to estimate the number of blood vessels per unit area via image analysis and the intensity of VEGF staining via immunohistochemistry. Placental tissues were also collected on these days to evaluate VEGF mRNA expression. Placental VEGF mRNA expression and the numbers of blood vessels per unit area of placental and adjacent endometrial tissue were low and decreasing from Day 25 to Day 44, before increasing (P < 0.05) markedly and progressively through Day 112. These data are consistent with the marked increase in VEGF immunostaining in the chorionic and uterine luminal epithelium from early to late gestation. Further, these increases in placental VEGF mRNA were positively correlated with fetal weight (r = 0.73; P < 0.0001) and placental efficiency (fetal weight/placental weight ratio; r = 0.66, P < 0.0001). These data are consistent with a role for VEGF in increasing the number of blood vessels at the placental endometrial interface, resulting in an increased capacity for nutrient transfer from the maternal to the fetal compartment.