An adequate hemostatic balance is mandatory to get successful pregnancy. Obstetric complications, such as recurrent pregnancy loss (RPL), might be due to an impairment of placental perfusion possibly related to an underlying prothrombotic status. In this study, we used the global coagulation assay, calibrated automated thrombography and traditional coagulation assay to search for a possible underlying hypercoagulable status in women with history of RPL compared with uneventful pregnancy women. Thrombin generation, Fibrinogen, factor VIII (FVIII), Plasminogen Activator Inhibitor-1 (PAI-1) and von Willebrand factor levels were analyzed in 92 not pregnant unexplained RPL and 64 uneventful pregnancy women. In RPL women, significantly higher fibrinogen, FVIII and PAI-1 levels, and thrombin generation with respect to those observed in uneventful pregnancy women were found. By dividing the study population into quartiles of endogenous thrombin potential (ETP), a lower percentage of RPL women than uneventful pregnancy women in the second quartile was observed, whereas a higher percentage of RPL in comparison with uneventful pregnancy women in the third and fourth quartile was found (P = 0.009). Accordingly, the cut-off ETP of 1222.1 nmol/l was chosen; ETP above cut-off concentration was associated with more than two-fold increased risk of RPL (P = 0.008), also after adjustment for traditional risk factors (P = 0.009). We provided evidence of an underlying alteration of vascular network related to increased coagulation components, and fibrinolysis inhibitor levels in healthy women with history RPL; therefore, calibrated automated thrombography global assay and testing for FVIII and PAI-1 would be advisable in clinical practice to evaluate the hypercoagulable status in RPL women planning future pregnancy.