Prosthetic valve endocarditis is a potential complication of valve replacement surgery and warrants prompt diagnosis and appropriate treatment. Thus, the blood culture in addition to providing an etiological organism is important in establishing appropriate antibiotic therapy. A case of prosthetic valve endocarditis (PVE) is presented with repeatedly negative blood cultures at a community hospital and refractory to prolonged therapy with standard antibiotic regimens. Appropriate workup eventually identified the causative organism as Legionella pneumophila, and antimicrobial therapy directed against Legionella combined with a repeat valve replacement effectively treated this case. Aspects of culture-negative PVE including the microbiology and etiology are discussed. Legionella endocarditis represents an important cause of culture negative PVE and should be considered in the differential diagnosis of culture negative PVE refractory to standard antimicrobial therapy.