Aim. To compare the effectiveness and safety of thrombolytic therapy of massive pulmonary embolism with the use of a tissue plasminogen activator, alteplase, and a fibrin non-specific agent, urokinase. Material and methods. The present comparative prospective non-randomized study included 71 patients presenting with massive pulmonary embolism (PE). The patients were allocated to two groups depending on the class of the thrombolytic preparation used for the treatment of PE. Thirty patients were given urokinase and 41 were treated with alteplase. The effectiveness of therapy was estimated by computed tomography of the pulmonary arteries with the use of the bolus tracking technique, angiopulmonography, lung perfusion scintiography, and echocardiography. Results. Thrombolytic therapy (TLT) proved beneficial for 56 (78.8%) patients. In the group treated with alteplase, therapy had the favourable outcome in 31 (75.6%) patients compared with 25 (83.3%) cases in the group treated with fibrin non-specific thrombolytic preparation (FNSP). The two groups were not significantly different in terms of lethality rate (9.7% and 6.6% respectively, p=1.0), the overall lethality being 8.4%. The complete recovery with thenormalization of hemodynamics in the pulmonary circuit was documented in 12 (40%) patients in the FNSP group and in 6 (14.6%) cases in the alteplase group (p=0.025). The partial recovery with a reduction of systolic pressure in the pulmonary artery to 35-45 mm Hg occurred in 16 (53.3%) and 27 (73.1%) patients respectively (p=0.33). Specifically, mean systolic pressure in the pulmonary artery decreased from 53.0±4.7 mm Hg before TLT with urokinase to 35.0±7.8 mm Hg after the treatment. The same parameters were 54.9±4.8 mm Hg and 35.3±4.0% before and after TLT using alteplase respectively (p=0.69). Four (16.6%) cases of hemorrhagic complications were documented in the FNSP group compared with 6 (19.5%) in the alteplase group. Thrombolysis had to be discontinued in two cases of hemorrhagic complications in the former group and in all such cases in the latter group. Conclusion. Urokinase therapy proved more affective than TLT with alteplase for the treatment of massive pulmonary embolism. The two modalities resulted in complete normalization of pulmonary circulation in 40 and 14,6% of the patients respectively (p=0,015). In gives reason to recommend urokinase as the principle thrombolytic agent for the treatment of massive pulmonary embolism.