Catheter-based large bore mechanical thrombectomy strategies for treating pulmonary embolism (PE) aim to quickly remove thrombus and relieve right ventricular (RV) strain. Such approaches involve the mechanical removal of thrombus from the pulmonary arteries by aspiration or entrapment. Interest in these techniques has stemmed from their rapid improvement of hemodynamics, reduced bleeding risk, and lack of intensive care unit requirement relative to thrombolytic-based treatments. Mechanical thrombectomy represents a safe alternative for PE patients with contraindications to thrombolytic therapy, which can occur in up to 50% of patients, and may be more effective at treating older thrombus, which can be resistant to thrombolytic drugs. Several devices have been developed with variations on these mechanisms-of-action. The FlowTriever System (Inari Medical, Irvine, CA) and Indigo Aspiration System (Penumbra Inc, Alameda, CA) are the most studied medium-to-large bore devices indicated for treatment of PE. The FlowTriever System is comprised of the Triever aspiration catheter (16F, 20F, and 24F diameter) and optional FlowTriever disks which can be used to disrupt and entrap thrombus. The safety and efficacy of the FlowTriever System has been evaluated in the FLARE IDE study; the ongoing prospective, multicenter FLASH registry; in high-risk patients in the FLAME registry; and in ongoing PEERLESS and PEERLESS II randomized controlled trials (RCTs). The Indigo Aspiration System consists of an aspiration catheter (12F and 16F diameter) connected to a computer-assisted aspiration engine that controls a continuous aspiration based on the detection of thrombus. The Indigo System has been evaluated in the EXTRACT-PE IDE study; the ongoing prospective, multicenter STRIKE-PE registry; and the ongoing STORM-PE RCT. Data from these ongoing RCTs should provide high-quality evidence to inform societal treatment guidelines regarding PE management in the years to come.