Burkholderia cepacia prosthetic valve endocarditis (PVE) is extremely rare, with few cases in the literature. A report of a patient with PVE is described, followed by a literature review on B. cepacia PVE. A 38 year old man with poor dentition and a history of intravenous drug use (IVDU) and mitral valve replacement was found to have a mitral valve vegetation. Five sets of blood cultures on different days grew B. cepacia. Individual sets of blood cultures on different dates also isolated S. viridans (outside hospital culture), methicillin-resistant S. epidermidis (hospital day 1), and Bacillus spp. (hospital day 6). He was successfully treated with ceftazidime and levofloxacin as dual therapy for B. cepacia PVE, in addition to vancomycin for gram positive coverage. This case report and review highlights the possibility of B. cepacia PVE in immunocompetent patients with poor dentition, with the potential for a successful outcome following combination antimicrobial therapy.