The Endogenous Thrombin Potential (ETP) is a plasma assay, which measures the effect of activated protein C (APC) on thrombin generation via the activation of the extrinsic coagulation pathway with tissue factor. The result is expressed as a normalized sensitivity ratio (APC-sr). Abnormality of the protein C pathway, such as Factor V Leiden mutation, produces a high ETP result, in contrast to the aPTT-based activated protein C resistance (APCR) assay. Recent studies have consistently shown an increase in APC-sr with the use of oral contraceptives, more with third than second generation preparations. This observation combined with epidemioiogic studies that suggested the former type of contraceptive was more thrombogenic than the latter, generated the hypothesis that abnormalities in ETP were associated with venous thromboembolism (VTE). To determine if increase ETP is associated with VTE, with studied 118 unselected patients with suspicion of a first VTE; 98 were women and 20 were men. The diagnosis of VTE was confirmed in 9 women and also in 9 men. Twenty-nine women were using hormone replacement therapy (HRT) while 69 were not users. Patients were tested for APCR or Factor V Leiden, and affected patients were excluded. APC-sr results were divided in 6 groups based on sex, VTE and HRT status: N Mean SD Median women vte - hrt - 64 2.39 1.10 2.18 women we - hit + 25 2.96 0.85 2.84 women vie + hrt - 5 2.55 1.44 2.44 women vte + hrt + 4 2.60 2.20 1.85 men vte- 11 3.02 2.56 1.92 men vte + 9 2.65 1.40 2.28 Women using HRT showed significantly higher results of APC-sr than non-users. However, because of the small number of patients with acute VTE, we were unable to show elevated APC-sr levels in this group. After log-transformation of the data (because of significant skewness of data distribution), we proceeded to multiple logistic regression analysis to assess the role of APC-sr as a predictor of acute VTE, after adjustment for sex, HRT status and cancer. Based on this analysis, APC-sr does not appear to predict VTE (OR: 0.58; 95% CI: 0.15-2.2). In conclusion, this study fails to demonstrate an association between the ETP assay and acute VTE. Further studies with larger number of patients should be performed for definitive results.