Abstract: Prosthetic valve endocarditis is a serious medical condition, which may lead to significant morbidity and potentially fatal end result. At times, diagnosis is difficult when echocardiographic modalities fail to detect the presence of vegetation or abnormality on the valve itself or adjacent cardiac tissues. In addition, both early- and late-onset diseases may, on occasion, involve unusual microorganisms that not only can be challenging to cultivate but also lack specific treatment guidelines. Bordetella holmesii, a relatively recent addition to the Bordetella genus, has rarely been associated with clinical infection, presenting most often as bacteremia, or less frequently, respiratory illness. Generally, individuals manifest mild disease when infected with these somewhat avirulent gram-negative coccobacilli. However, endocarditis has been diagnosed in 3 previously reported cases. Most of the patients with B holmesii infection have been young and immunocompromised, almost always as a result of anatomical or functional asplenia. We describe the first reported case of prosthetic valve endocarditis due to B holmesii, diagnosed in an elderly immunocompetent man; apropos, we review the pathogen B holmesii, including a summary of known previous infections and discuss its clinical manifestations, microbiologic characteristics, and potential treatment options.