There is thus far no apparent tendency toward the reduction in the incidence of venous thromboembolism (VTE) despite the active worldwide campaign for prophylaxis of this condition. A separate challenge is intrahospital thrombosis that especially frequently complicates the postoperative course in the patients of high-risk groups. Such groups are highly heterogeneous and characterized by the venous thrombosis rate ranging in a broad range (mean around 12%). The results of the recent studies permits to  distinguish in the standard high-risk group the subjects highly predisposed to the development of thrombosis (the subgroup at «extremely high risk» of thrombosis) the frequency of which can be as high as 50%. This subgroup includes the patients with ≥3 individual predisposing conditions. A more sophisticated tool for the identification of the new subgroup is the Caprini scale allowing to include in it  the patients with ≥11 score regardless of the  profile of the disease. The modified protocol for VTE prophylaxis was proposed for the patients of this subgroup including elastic compression of the lower extremities up to the pressure of 40 mm Hg, electrical muscle stimulation (EMS) in the lower legs, and the application of unfractionated heparin at a dose on the order of 300 U/kg in day  selected on an individual basis. All these methods proved to be highly efficacious even though their effectiveness differed in the patients of different risk groups. Specifically, the reduction of risk could not be observed in the patients with the predominance of the active oncological process due to its initially low level owing to the high effectiveness of  the standard preventive measures. The electrical muscle stimulation produced the especially pronounced positive effect in the  patients with paralysis of the lower extremities. At the same, the patients presenting with sepsis equally benefited from EMS and elevated doses of heparin. Compression, in its turn, was relatively inefficient regardless of the predominant risk factors. It is concluded that the present study has for the first time demonstrated the relationship between the effectiveness of the concrete prophylactic measures and selected risk factors which provides a basis for the development of the personalized systems for prophylaxis of postoperative venous thromboembolism.