A bloodstream infection in a patient with a recently implanted prosthetic cardiac valve is an ominous sign. In the six studies reviewed, the overall mortality rate for patients with bloodstream infections with and without prosthetic valve endocarditis (PVE) were 48% and 51%, respectively. Patients with PVE usually die from a complication of endocarditis. The high mortality rate in patients without endocarditis can be attributed to a severely ill cohort of hospitalized patients, who have a prolonged postoperative course and require life support in intensive care units for multiple organ failure. Although gram-positive cocci (especially coagulase-negative staphylococci) are the most common organisms associated with PVE, any microorganism isolated from the bloodstream must be considered as a potential cause of endocarditis in patients with prosthetic cardiac valves. The conclusion of earlier studies, that PVE was unlikely if infection was due to a gram-negative aerobic bacillus or if a portal of entry could be established, has not been supported by recent studies. An aggressive search for evidence of endocarditis must be performed in all patients with implanted heart valves and bloodstream infections. Successful treatment for most cases of early-onset PVE is primarily surgical.