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High‐risk acute pulmonary embolism (PE) is associated with significant in‐hospital mortality. Large‐Bore Mechanical Thrombectomy (LBMT) is a treatment option for acute PE, but data on its efficacy in high‐risk PE was limited. This prospective case series reported the outcomes of 14 patients with high‐risk PE treated using a novel multipurpose mechanical aspiration system (MMAS). Most patients were in hemodynamic decompensation, requiring inotropic or mechanical circulatory support. The mean procedural time was 73.5 ± 39.2 min. Complete procedural success was achieved in 78.6% of the cases, while two patients required bailout therapies. The mean pulmonary arterial pressure decreased by 27.2%, and the right‐ventricle/left‐ventricle ratio normalized in 85.7% of patients. The primary endpoint—in‐hospital mortality—was 0%, while the major bleeding rate was 27.2%. These findings suggest that MMAS is a safe and effective intervention for acute high‐risk PE.