The AngioVac System (AngioDynamics, Latham, NY) was developed for the treatment of right-sided heart and intravenous masses. Lately, it has been employed to deal with left-sided heart masses, in particular, native valve endocarditis (NVE) and valve prostheses endocarditis (VPE) in high-risk patients. Left-sided heart endocarditis has a high morbidity, and it also has a high mortality when open heart surgery is performed. Recently, patients presenting with left NVE and VPE have been treated with the off-label use of the AngioVac System even if the solution presents a considerable cerebral embolization risk issue due to the risk of fragmentation rather than a complete en-bloc aspiration of the masses. A percutaneous cerebral embolism protection system is currently used in TAVI procedures, especially when the native valve presents extensive calcifications and consequent significant embolic risks. We hereby present a clinical case series of a combined utilization of the AngioVac System and cerebral embolism protection system Triguard (Keystone Heart Ltd., Herzliya, Israel) to treat left NVE and VPE in prohibitive-surgical-risk patients.