Vascularity is increased in placentae from high as compared to low altitude pregnancies. An angiogenic response to hypoxia may protect an organ from further hypoxic insult by increasing blood flow and oxygen delivery to the tissue. We hypothesized that increased placental vascularity is sufficient to adapt to high altitude. Therefore, indices of hypoxic stress would not be present in placentae from successful high altitude pregnancies. Methods: Full-thickness placental biopsies were A) collected and frozen in liquid nitrogen within 5 minutes of placental delivery and B) fixed in formalin for stereologic analyses, at high (3100 m, n = 10) and low (1600 m, n = 10) altitude. HIF-1 activity was analyzed by enzyme-linked immunoabsorbance assay (ELISA). Western blot analyses were used to evaluate HIF-1, HIF-1, HIF-2, von Hippel-Lindau protein (pvHL), VEGF, Flt-1, enolase, and GAPDH. Magnetic resonance spectroscopy (MRS) was used to evaluate endogenous metabolism. Results: The ratio of placental capillary surface density to villous surface density was 70% greater at high as compared to low altitude. HIF-1 activity and HIF-1 associated proteins were unchanged in placentae from high vs. low altitude pregnancies. Placental expression of HIF-1-mediated proteins VEGF, Flt-1, enolase, and GAPDH were unchanged at high vs. low altitude. Succinate, GSH, phosphomonoesters and ADP were elevated in placenta from high as compared to low altitude. Conclusion: Placentae from uncomplicated high altitude pregnancies have greater vascularity and no indication of significant hypoxic stress at term as compared to placentae from low altitude.