OBJECTIVES: Device-related thrombus (DRT) remains a significant complication in the field of left atrial appendage occlusion (LAAO). In patients who have difficulty tolerating long-term anticoagulation, treatment options are limited. We present a step-by-step intracardiac echocardiography (ICE)-guided AngioVac (AngioDynamics) challenging case in a 71-year-old woman with a gastrointestinal bleeding tendency and a highly mobile thrombus on a Watchman FLX device (Boston Scientific). KEY STEPS: We obtained a 26-F DrySeal (Gore Medical) venous access, a 15-F extracorporeal membrane oxygenation cannula arterial access, and a 3-dimensional ICE access. We performed a challenging transseptal crossing using an Agilis medium curl catheter (Abbott) and an electrified Astato wire (Asahi Intecc Medical) as a result of a severely hypertrophic lipomatous septum. We snared the ICE catheter across the interatrial septum (IAS) with a 35-mm gooseneck snare in the inferior vena cava. We used a balloon-assisted technique to bring the F-18 AngioVac system across the IAS. The helicoptering technique with a J-wire assisted with suction of the DRT. POTENTIAL PITFALLS: Currently, there are no data to support which post-LAAO antithrombotic regimen predicts DRT. For patients who are unable to tolerate long-term anticoagulation, treatment options are limited. To our knowledge, this is the first reported ICE-guided LAAO thrombus aspiration. TAKE-HOME MESSAGES: ICE-guided aspiration thrombectomy of LAAO thrombus is feasible in high-risk patients who cannot tolerate long-term oral anticoagulation and to reduce the risk of clot embolization.