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Nonvalvular cardiovascular device infections, although rare in most cases, represent substantial clinical challenges due to their life-threatening potential and diagnostic complexity. Although infections associated with prosthetic valves, cardiovascular implantable electronic devices, vascular grafts, and mechanical circulatory support devices have garnered considerable attention and specific guidance, infections of other nonvalvular cardiovascular devices have not. Therefore, this Science Advisory focuses on a contemporary profile of other nonvalvular device infections and includes an algorithm for their evaluation in patients with bloodstream infection, which is common, particularly among older individuals.