Bartonella quintana is a relatively rare cause of endocarditis in the United States (USA). Historically it was linked with trench fever, but cardiac involvement seems to be more prevalent recently. There are some known risk factors associated with Bartonella quintana endocarditis such as human immunodeficiency virus (HIV) infection, alcoholism, homelessness and poor hygiene. We report a case of 37-year-old African man, with culture negative endocarditis, emboli and rising B. quintana and B. henselae IgG titers. B. quintana DNA was subsequently detected from the mitral valve sample with 16S rRNA gene and ribC primer sets. Eventually, blood culture for B. quintana was positive after 21 days. Patient was successfully treated with doxycycline and gentamicin. There have been a few cases of B. quintana endocarditis in the USA and most of them were associated with HIV infection, homelessness or alcoholism. The case reported here highlights the importance of high clinical suspicious for Bartonella species in blood culture negative endocarditis in the USA in appropriate setting and will help to increase awareness among physicians for early diagnosis and treatment.