Postpartum deep vein thrombosis is believed to be related to increased activation of the hemostasis system at the time of delivery. To date, studies designed to test this hypothesis have had relatively small sample sizes or used the measurement of specific coagulation factors and functional tests reflecting hemostasis activity in vitro. With the use of recent technologic advances we determined the effect of delivery on hemostasis in vivo by measuring 11 hemostatic indices simultaneously in 70 healthy pregnant women. Significant increases were found in fibrinopeptide A (p < 0.001), β-thromboglobulin (p < 0.001), and platelet factor 4 (p < 0.001), suggesting maximum platelet activation and fibrin formation at the time of delivery. In addition to continued clotting activity at 3 hours post partum, increased D-dimer, fibrin-fibrinogen degradation products, and decreased α2-antiplasmin levels suggest maximum fibrinolysis. These changes reflect a peak in hemostatic activity at delivery and in the immediate postpartum period that may predispose the development of deep vein thrombosis. © 1990.