In recent years, there has been a shift in the epidemiology of patients with infective endocarditis (IE). This has been characterized by an alarming increase in IE in patients who inject drugs, cardiac implantable electronic device–related IE, and those with comorbid conditions and high surgical risk. This unmet need has mandated a reevaluation of complex management strategies in these patients and introduction of unconventional approaches in treatment. Percutaneous mechanical aspiration has emerged as both a diagnostic and therapeutic option in selected patients with IE.