Injection drug use is an important risk factor for endocarditis. The clinical manifestations of endocarditis associated with injection drug use differ from those in person who do not use drugs. Endocarditis in drug users more often affects the right side of the heart and presents with fever and pulmonary emboli rather than left-sided emboli. Blood cultures and echocardiography are the mainstay of diagnosis; these tests are particularly helpful in identification of endocarditis associated with injection drug use because of the high frequency of right-sided valvular involvement and the low incidence of culture-negative endocarditis in this population. Since staphylococcal species are the dominant causative organism, penicillin and an aminoglycoside are the treatments of choice. Injection drug users with left-sided endocarditis or with symptomatic human immunodeficiency virus infection have poor prognoses.