There are few case reports of infections caused by Brevibacterium species, and there have been no previously reported cases of endocarditis caused by any of the 6 known species of Brevibacterium. We report the first case of Brevibacterium endocarditis (caused by Brevibacterium otitidis) in a patient with prosthetic heart valves. The patient responded to 6 weeks of treatment with vancomycin and 2 weeks with gentamicin, and she has been receiving long-term maintenance therapy with oral azithromycin.