Although dysfunctional endothelium, vasoconstriction, and in situ thrombosis are characteristics of primary pulmonary hypertension, the role that plasma vasomotor and coagulation factors play in this phenomenon are not completely understood. The aim of this work was to ascertain the diagnostic value of endothelin-1, thrombomodulin, tissue factor, and tissue factor pathway inhibitor, as well as their correlation with endothelial dysfunction in primary pulmonary hypertension patients. We analyzed the plasmatic concentration and chromogenic of the above-mentioned molecules using immunoenzymatic techniques. Patients were divided into responders and nonresponders on the basis of their hemodynamic response to a vasodilator trial. We found a continuous increase in endothelin-1 levels and a continuous decrease in functional tissue factor in the control group, responders, and nonresponders, respectively. Moreover, the patients showed a moderate decrease in thrombomodulin levels compared with the control group, without statistical significance. These results support a previous description of a decrease in thrombomodulin levels in primary pulmonary hypertension patients and suggests that an alteration of endothelin-1 and functional tissue factor could be related to a worsening of endothelial function and, indirectly, with the clinical severity of primary pulmonary hypertension.