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Clinical economic analysis of the use of enoxaparin, rivaroxaban and dabigatran etexilate for venous thromboembolism prophylaxis (VTP) in patients after vast orthopaedic operations within the RF public health system was performed. For cost calculation the modelling of decision tree where the presence/absence of clinically significant hemorrhages as the index of anticoagulant safety and VTP incidence as efficacy index were considered. The model was based on the meta-analysis of the published randomized studies results and indirect comparison performed using those data. Only direct medical costs were taken into account. Anticoagulant therapy costs were calculated for the drug dosing regimen according to the use instructions registered in RF. The time horizon of the model was in line with the average duration of thromboprophylaxis after orthopaedic operations: 21 day for enoxaparin and dabigatran, and 25 days for rivaroxaban. Determinate analysis of sensitivity including the evaluation of clinical and economic efficacy of drugs after either total hip or knee arthroplasty was performed. Total costs per patient made up 11 486.99 rub for enoxaparin, 9 035.07 rub for dabigatran and 6 172.63 rub for rivaroxaban use. During sensitivity analysis rivaroxaban preserved its advantage in all scenarios. Rivaroxaban is a preferable drug for VTP prophylaxis after vast orthopaedic interventions as with higher clinical efficacy it requires lower costs.