- Preterm labor (PTL) has been associated with an increased thrombin generation in the maternal circulation and amniotic fluid. Tissue factor (TF) is a potent initiator of the coagulation cascade, which can trigger the hemostatic system to generate thrombin. The aims of this study were to determine whether spontaneous PTL with intact membranes is associated with changes in the maternal plasma concentrations and activity of TF as well as tissue factor pathway inhibitor (TFPI). This cross-sectional study included women in the following groups: (1) normal pregnancies (n = 86); (2) term pregnancies in spontaneous labor (TIL) (n = 67) and not in labor (TNL) (n = 88); and (3) patients with spontaneous PTL and intact membranes (n = 136) that were classified into three sub-groups: (a) PTL without intra-amniotic infection and/or inflammation (IAI) who delivered at term (n = 49); (b) PTL without IAI who delivered preterm (n = 54); and (c) PTL with IAI who delivered preterm (n = 33). Plasma concentrations of TF and TFPI were measured by ELISA, and their activity was measured by chromogenic assays. Non-parametric statistics were used for analysis. (1) Among women at term, those with spontaneous labor had a higher median maternal plasma TF and a lower median TFPI concentration than those without labor. (2) Patients with PTL had a significantly lower median maternal plasma TFPI concentration than that of normal pregnant women, regardless of the presence of IAI. (3) There was no significant difference in the median maternal plasma TF concentration between patients with a normal pregnancy and those with PTL. (4) In contrast, the median maternal plasma TF activity was higher among patients with PTL than in women with normal pregnancies, regardless of the presence of IAI or preterm delivery. (5) However, maternal plasma TFPI activity did not differ among the study groups. Women with preterm parturition, in contrast to those in labor at term, have a higher TF activity and a lower TFPI concentration, without a significant change in the median maternal plasma TF concentration. These observations suggest that the increased thrombin generation reported in patients with PTL may be the result of activation of the extrinsic pathway of the coagulation cascade. In addition, the increased thrombin generation reported in patients with PTL could be due to insufficient anti-coagulation, as reflected by the low maternal plasma TFPI concentration.