We have studied if serum levels of soluble fms-like tyrosine kinase-1 (sFlt-1) and placenta growth factor (PlGF) in pregnancy could predict excess post-partum bleeding. In 392 normotensive singleton pregnancies, concentrations of sFlt-1 and PlGF in the first, second, and third trimester were compared between women with and without excess post-partum bleeding, defined as blood loss volume of at least 500 mL. Mean concentrations of sFlt-1 were consistently higher in all three trimesters among women who had excess post-partum bleeding compared to women without this, but significantly higher only in the second trimester. For PlGF, there were no significant differences between the groups. High concentrations of the anti-angiogenic factor sFlt-1 in maternal circulation during pregnancy may be associated with an increased risk of excess post-partum bleeding.