In intrauterine growth restriction (IUGR), a subset of pregnancies undergoes placental vascular dysregulation resulting in restricted blood flow and fetal hypoxemia. Altered transcription of hypoxic regulated plasminogen activator inhibitor 1 (PAI-1) has been associated with pregnancy complications and angiogenic regulation. Here we assessed circulating PAI-1 as an indicator of placental insufficiency. Venous umbilical PAI-1 of hypoxemic (VpO2 20 versus 35 mmHg, p<0.0001) placental insufficient pregnancies (resistance index 0.9 versus 0.63, p<0.05) (n=18) was compared to controls (n=12). PAI-1 was increased (~10-fold, p<0.001) and had a positive predictive ratio of 6.7. Further, PAI-1 levels correlated to blood oxygen (r=-0.68, p<0.0001). The plasma’s angiogenic potency measured in vitro was associated with umbilical cord blood PAI-1 levels (r=0.65, p<0.01). This association was attenuated by PAI-1 inhibiting antibody (p<0.001). The results demonstrate PAI-1 as a potential marker of placental insufficiency and identify its close association with pathological hypoxia and angiogenesis in a subset of growth restricted pregnancies.