Aims: Thrombolysis and anticoagulation were the main treatment methods for acute pulmonary embolism. Anticoagulation therapy is recommended in the guidelines for patients with intermediate-low and low-risk PE, and emergency thrombolysis is recommended for high-risk or massive PE, in order to stabilize hemodynamics and reduce early mortality. Warfarin has been the anticoagulant of choice for pulmonary embolismHowever, there remains controversy about the treatment of acute intermediate-high-risk PE.Novel oral anticoagulants (NOACs) are increasingly used as an alternative. The study was aimed at assessing efficacy and safety of new oral anticoagulants (NOACs) after thrombolysis versus warfarin treatment on echocardiographic parameters and clinical outcome during hospitalization and in six mounth after admission, in patients with acute intermediate-high-Risk Pulmonary Embolism. Although the use of thrombolysis has been investigated in these patients, anticoagulation remains the standard treatment approach. Rivaroxaban and apixaban have shown similar efficacy and, in some cases, reduced major bleeding compared with standard approaches for acute treatment. The direct oral anticoagulants do not require regular coagulation monitoring. Methods: Consecutive patients (study court: age 42-85 years), with a episode acute pulmonary embolism,with onset of symptoms since no more than 6 hours, normal blood pressure ( >95 mmHg), right ventricle dysfunction (RVD) at echocardiography and positive lung spiral CT were in double blind fashion randomized: a group received 100 mg of alteplase (10-mg bolus, followed by a 90-mg i.v. infusion over a period of 2 hours) and warfarin after 48-72 h in according with INR target , and a group received 100 mg of alteplase (10-mg bolus, followed by a 90-mg i.v. infusion over a period of 2 hours) and NOACs (rivaroxaban or apixaban on randomization 1:1) after 48-72 h. In addition to alteplase , both groups received unfractionated heparin treatment for 48 h. Echocardiogram was performed at entry and 48 or 72, discharge and 6 months after randomization. Results: 44 patients were included in the study, 22 assigned to warfarin and 22 to NAOCs. The 2 groups were well matched with regard to features and clinical presentation. NAOCs group showed an safety and a reduction in clinical events during hospitalization and follow up was also observed. Conclusions: Our data suggest that NOACs after thrombolysis a favorable trend in clinical outcome and could merit consideration in patients with acute intermediate-high-Risk Pulmonary Embolism. The new anticoagulation have been shown to reduce the risk of recurrent venous thromboembolism when given for 6 months. This use after thrombolysis, at this time, is off‑label and should could be considered and included in the new guidelines.