Changes in the coagulation and fibrinolytic systems during pregnancy lead to a higher risk of thromboembolism. These changes include the increase of many clotting factors, as well as a significant fall in activity of fibrinolytic proteins, such as protein C. Protein Z is a vitamin-K-dependent plasma glycoprotein and inhibits the activation of factor X by serving as a cofactor to a plasma proteinase inhibitor. Protein Z deficiency has recently been reported in women with unexplained early fetal losses, and antibodies to protein Z can contribute to adverse pregnancy outcomes. The aim of this study was to determine the range of protein Z in normal pregnancies at different gestational weeks in a cross-sectional and a longitudinal setting. In the longitudinal study we found a 20% increase (p=0.006) of protein Z from first trimester to delivery and a 30% decrease (p<0.0001) 6 to 12 weeks after delivery. In the cross-sectional study these findings were reproducible. In summary, our data show a progressive increase in protein Z levels with gestational age in normal pregnancies and a return to normal levels around 6 to 12 weeks postpartum. The normal increase of protein Z during pregnancy may balance the increase of clotting factors to protect pregnant women from thrombosis.