Pulmonary embolism (PE) remains a leading cause of cardiovascular mortality worldwide, with an estimated incidence of 60 to 70 cases per 100,000 individuals annually (Konstantinides et al., 2020). Despite advances in risk stratification and therapeutic approaches, significant challenges persist in optimizing treatment strategies, particularly regarding thrombolysis, catheter-directed therapies, and long-term anticoagulation management. The REAL-PE II and OPTALYSE 3D studies provide critical insights into optimal thrombolytic strategies and catheter-based interventions. REAL-PE II aims to use a large propensity-matched real-world dataset to investigate the relative safety of different catheter-based technologies in contemporary PE management across the United States. Building on the findings of the previous SEATTLE-3D and OPTALYSE-PE studies, OPTALYSE-3D aims to investigate the effect of lytic dosing with catheter-based therapies on reperfusion of the distal pulmonary vasculature using a 3D reconstruction technique. These studies provide critical data to support safer, more effective interventional approaches.