A 76-year-old woman presented with a one-week history of dyspnea on minimal exertion and at rest. In the emergency room she underwent echocardiography and thoracic computed tomography scan with diagnosis of bilateral pulmonary embolism. Due to right ventricular dilatation and increasing values of NT-probrain natriuretic peptide, both markers of high risk that classify pulmonary embolism as "submassive" according to current international guidelines, we opted for thrombolysis. The patient underwent intra-arterial bilateral pulmonary thrombolysis facilitated by ultrasound, the first case in Italy. The patient recovered from pulmonary embolism after 10h of therapy, with improved gas exchange and symptoms. Subsequently, she developed arterial bleeding at the puncture site, due to accidental puncture of a branch of the femoral artery. The patient was treated with percutaneous embolization and transfusions. In patients with pulmonary embolism, even if not massive, thrombolysis should be considered, especially in the presence of high-risk markers. Direct intra-arterial pulmonary thrombolysis, facilitated by ultrasound, is an effective procedure that provides an alternative to conventional thrombolysis with the advantage of a lower thrombolytic dose.