The compliance with protocols of prophylaxis of venous thromboembolic complications significantly reduces their frequency even though does not completely prevents their development. One of the causes underlying the enhanced probability of venous thrombosis and pulmonary embolism is genetic mutations and polymorphism of factors of the blood coagulation and anti-coagulation systems. In this paper, we discuss three cases of pulmonary embolism in the immediate post-traumatic period in the patients suffering lower extremity long-bone fracture who were treated with adequate preventive anticoagulant therapy. Material and methods. The method of enzymatic amplification of polymorphic FV Leiden, PRT (FII), MTHFR, PAI-1, and NOS3 loci was employed to perform retrospective genotyping of three patients with lower extremity long-bone fracture and verified pulmonary embolism. Results and discussion. In all three cases, direct anticoagulants were used for prophylaxis of venous thromboembolic complications in accordance with the current recommendations. All the patients developed pulmonary embolism in the post-traumatic period that resulted in the death of two of them. Genotyping has shown that all the patients were heterozygous carriers of the MTHFR (677CT), NOS3 genes while being homo- and heterozygous for the 4G/5G PAI-1 gene. It means that their thrombophilia was due to genetic defects in the vascular-thrombocytic segment of hemostasis. In other words, the effectiveness of traditional prophylaxis of venous thromboembolic complications is impaired in the case of hereditary predisposition to thrombophilia. Conclusion. One of the methods for the improvement of the effectiveness of prophylaxis of thromboembolic complications in the patients suffering injuries or undergoing planned surgical interventions may be genotyping for the choice of adequate anticoagulant therapy on an individual basis.