Placental Growth Factor (PlGF) is an angiogenic and vasoregulatory peptide member of the vascular endothelial growth factor family. Reduction of free, circulating PlGF is associated with preeclampsia and fetal growth restriction, and precedes the clinical manifestations of disease by several weeks. It is not known whether aberrant PlGF is related for alterations in endothelial vascular function that cause or exacerbate the placental syndromes of pregnancy. We sought to determine if mid-pregnancy PlGF was related to, and possibly mediating, measures of maternal, fetal, or uterine hemodynamic function in women at risk for placenta-mediated complications of pregnancy. We measured free plasma PlGF (Triage PlGF Assay, Alere, Inc.) between 22 and 25 weeks in high risk subjects referred for assessment of fetal growth and uterine artery Dopplers due to abnormalities of serum screening analytes or other risk factors for preeclampsia. Maternal hemodynamic parameters including mean arterial pressure (MAP), cardiac index (CI), systemic vascular resistance (SVR) and index of contractility (ICON) were measured in recumbent position with noninvasive electrical cardiography (Aesculon EC System, Cardiotronics, Inc.). Doppler measurements of blood flow in the uterine arteries (pulsatility index, PI) and umbilical artery (systolic:diastolic ratio, S/D) were obtained by ultrasound (Voluson E8, GE Healthcare, Inc.), along with the estimated fetal weight (EFW). PlGF was expressed as the log concentration, plotted against the hemodynamic measurements, and analyzed with Spearman's correlation coefficient, R. Statistical significance was set to p=0.05. Data from seventeen fully studied patients were analyzed. The median gestational age was 24.3 weeks. PlGF concentration ranged from 25 to 1180 with a median of 235pg/ml. PlGF was positively related to maternal cardiac index (R=0.56, p=0.02) and ICON (R=0.51, p=0.04) and negatively related to SVR (R=-0.48, p=0.05). There was a non-significant negative correlation with MAP (R=-0.41, p=0.10). PlGF showed a positive correlation to EFW (R=0.52, p=0.03) and a negative relationship to umbilical artery S/D ratio (R=-0.42,p=0.06). There was no correlation between maternal PlGF and uterine artery Doppler PI (R=-0.19, p=0.46). The concentration of circulating free PlGF at mid-pregnancy is related to both maternal systemic hemodynamic function and fetal umbilical artery resistance (and growth) in high risk pregnancies prior to the onset of preeclampsia. It is not, however, related to vascular resistance in the uterine artery. PlGF may play a role in modulating the general vascular function of the fetus and mother after establishment of the uteroplacental circulation.