Percutaneous mechanical aspiration has emerged as a novel, catheter-based strategy for the management of right-sided infective endocarditis, particularly in patients with a suboptimal response to antimicrobials or in those considered high risk for surgery. Initially developed for thrombus extraction, percutaneous mechanical aspiration has been increasingly used to achieve source control by debulking large vegetations. Despite growing clinical adoption and support from societal statements and guidelines, there have been no randomized controlled trials evaluating its safety or efficacy in right-sided infective endocarditis. Current evidence is derived from retrospective case series, registries, and administrative data sets, all limited by heterogeneity in patient populations, procedural techniques, and outcome definitions. Nevertheless, recent data from multicenter registries demonstrate promising procedural success and feasibility in select patients. In response to expanding use and persistent knowledge gaps, this American Heart Association Science Advisory aimed to (1) define the rationale and evolving indications for percutaneous mechanical aspiration in right-sided infective endocarditis, (2) summarize the available clinical evidence and technical considerations, (3) provide expert consensus on patient selection and procedural planning, and (4) identify priorities for future prospective investigation.