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Since the publication of the 2015 American Heart Association scientific statement on infective endocarditis, its incidence has increased, its epidemiology has changed, and novel diagnostic and treatment options have become available. Updated case definitions, non–culture-based pathogen identification methods, and advanced multimodality imaging techniques have emerged. A randomized controlled trial of partial oral therapy published in 2019 may change the treatment landscape for the foreseeable future. Percutaneous mechanical aspiration of right-sided vegetations is being used in select patients with uncontrolled infection despite appropriate antimicrobial therapy. The importance of an endocarditis team has become increasingly recognized in the management of this life-threatening syndrome. Therefore, multidisciplinary experts in cardiovascular infections were commissioned to develop this updated scientific statement on the diagnosis and management of infective endocarditis.