The objective of the present study was the evaluation of the safety and clinical effectiveness of endovascular mechanical fragmentation with local thrombolysis in the patients presenting with pulmonary embolism at intermediate and high risk of early death. The prognosis, outcome, and optimal treatment of acute pulmonary embolism (PE) strongly depend on the initial conditions of systemic hemodynamics. The electrocardiographic signs of right ventricular (RV) dysfunction and the positive results of cardiac biomarker testing in the patients with acute PE are independent predictors of the unfavourable outcome of this disease in the patients with stable hemodynamics. Also, they are associated with the enhanced risk of early death, the mortality rate amounting to 15%. The results of recent studies give evidence that the patients presenting with pulmonary embolism at intermediate and high risk of early death can be managed using a more aggressive treatment than anticoagulation (thrombolytic) therapy. The present study included 60 patients with acute PE at intermediate and high risk of early death. They were randomly allocated to two groups at the ratio of 2:1. The patients comprising group 1 were treated using an electromechanical filter (EMF) with local thrombolysis at half of the recommended dose (n=40) while the patients included in group 2 underwent standard anticoagulation therapy with heparin (n=20). This randomized study has demonstrated that the application of EMF with local thrombolysis is not only a safer but also clinically more efficient therapeutic modality than standard anticoagulation therapy for the management of the patients presenting with pulmonary embolism at intermediate and high risk of early death. None of the patients treated by the two methods developed either a clinically significant hemorrhage (CSH) or the specific complications, hemodynamic decompensation, and 30-day lethality. One year after the treatment, there were no cases of recurrence deep vein thrombosis (DVT) and/or acute PE in the patients of the first group whereas 6 (30%) patient of group 2 developed DVT/acute PE relapses (p<0.05; p=0.003). The formation of chronic thromboemolic pulmonary hypertension (CTEPH) was documented in 2 (5%) patients of group 1 and in 6 (30%) of group 2 (p<0.05; p=0.007). The survival rate among the patients comprising group 1 was significantly higher (100%) in comparison with 90% among the patients of group (p<0.05; p=0.004). It is concluded that the proposed method makes it possible to reduce the risk of adverse events by a factor of 8 during the long follow up period in the patients presenting with pulmonary embolism at intermediate and high risk of early death.