Although there are numerous causes of deep vein thrombosis (DVT), the exact cause of DVT may frequently be difficult to identify with certainty in daily routine. A decreased concentration of tissue factor pathway inhibitor (TFPI) as the only known inhibitor of the extrinsic pathway of coagulation has been implicated as a potential risk factor for DVT. The administration of heparin results in its increased plasma concentration. The mechanism of heparin antithrombotic action and differences in the action of unfractionated and low-molecular heparin (nadroparin) have not yet been fully clarified. Considering the issues stated above, the main objective was to assess the possible differences in the concentration of total and free TFPI between DVT patients treated with unfractionated heparin and those administered nadroparin. The aim was also to determine the possible correlation of TFPI (total and free) concentration with activated partial thromboplastin time (APTT) and differences in the concentration of total and unbound TFPI according to DVT patient age before and during the treatment with unfractionated heparin and nadroparin. The study included 100 patients with DVT diagnosed by two-dimensional color Doppler, divided into two groups of 50 patients: one group treated with unfractionated heparin and the other treated with nadroparin. Study parameters were determined before, and at 4 h and 48 h of therapy administration. Statistically significantly higher levels of free TFPI were recorded in DVT patients administered unfractionated heparin in comparison with those treated with nadroparin at 4 h and 48 h. At 4 h of therapy administration, the levels of free TFPI were statistically significantly higher as compared with the levels measured before and 48 h of therapy administration in both patient groups. There was no statistically significant difference between the levels of free TFPI measured before and 48 h of either unfractionated heparin or nadroparin administration. Between-group differences in total TFPI did not reach statistical significance. Total TFPI showed a statistically significant positive correlation with APTT before therapy in the group of patients treated with unfractionated heparin. In the group of patients treated with nadroparin, a significant positive correlation was found between freeTFPI and APTT at 4 h and 48 h, and between total TFPI and APTT at 48 h of therapy administration. In the group of DVT patients aged ≤50 administered unfractionated heparin, significantly higher levels of free TFPI were recorded at 48 h of therapy administration as compared with the age-matched group administered nadroparin. In the group of DVT patients aged >50 treated with unfractionated heparin, the levels of free TFPI were significantly higher at both 4 h and 48 h as compared with the patients age ≤ 50 and the age-matched group administered nadroparin. In comparison with nadroparin, study results showed the use of unfractionated heparin in the treatment of DVT patients to cause a statistically significantly greater increase in the level of free TFPI, which has an anticoagulant action, whereas differences in total TFPI were not statistically significant. At 48 h, the levels of free TFPI returned to pretherapeutic values in both therapy groups, possibly suggesting reduction of the factor reserve in DVT patients.