Introduction: Current treatment guidelines advocate for the aggressive management of both high-risk and subsets of moderate-risk pulmonary embolism (PE) with fibrinolytic therapy. However, there is limited evidence on the risks and benefits of fibrinolytic therapy in PE, with mortality improvement still to be proven. This study aimed to report the incidence of major bleeding and death after thrombolysis for PE. Methods: A health records review was performed on data from two hospitals between 2007 and 2017. Pharmacy identified all patients who had received either alteplase or tenecteplase. Trained abstractors reviewed each chart to determine the indication for thrombolytic therapy. Patients were included if they received systemic thrombolysis for diagnosed or presumed PE. Data was extracted on 30-day mortality, International Society of Thrombosis and Hemostasis defined major bleeding within 30 days, premorbid anticoagulant and antiplatelet prescription, age, sex, comorbidities, renal function, history of bleeding, type and dose of thrombolytic and category of PE (high or moderate risk). Results: 1534 patients were identified, of which 72 received systemic thrombolysis for PE. The median age was 57, 34 were male, 17 with a history of venous thrombosis and 12 with cancer. Fifty-four were classified as having high-risk PE, of whom 39 received cardiopulmonary resuscitation (CPR) when thrombolysis was administered. Formal confirmatory imagining for PE was obtained in only 23/39 patients who were in cardiac arrest. Eighteen patients were classified as moderate-risk PE. The incidence of major bleeding was 28/54 (52%, 95% CI 39-65%), and 3/18 (17%, 95% CI 6-39%) for the high and moderate risk groups respectively. There were 4 intracranial bleeds, all in the high-risk PE group. The only significant predictor of major bleeding was the need for CPR at the point of administration of the thrombolytic agent (OR 2.6, 95% CI 1.0-7.5, adjusted for age). Thirty-four patients died within 30 days (47%, 95% CI 36-59%), all in the high-risk PE group. Death was not associated with any demographic variable on univariate analysis. Death occurred in 28/39 (72%, 95%CI 56-83%) patients who received CPR and 6/33 (18%, 95% CI 9-34%) who did not. Conclusion: We found a high incidence of 30-day major bleeding and death following administration of thrombolysis for PE which will help inform future prognostic discussions in our institution.