The clinical significance of and the risk factors for persistent bacteremia were assessed in 299 episodes. Persistent bacteremia was defined as at least two positive blood cultures obtained on different calendar days during the same infectious episode. Short-term bacteremia was defined as positive blood cultures solely on the first day of the infectious episode. A total of 4,277 episodes of bloodstream infections were detected, of which 299 episodes (7%) were persistent bacteremia. The following were independent risk factors were for persistent bacteremia: burns, presence of a central vascular catheter, cirrhosis, infections caused by Salmonella spp., polymicrobial infections, and inappropriate empirical antibiotic treatment. Irrespective of the source of infection, the presence of a central vascular catheter was correlated with an increased risk for persistent bacteremia. Mortality among patients with persistent bacteremia was 50%, compared to 35% among patients with short-term bacteremia. Because of the high mortality associated with persistent bacteremia, a thorough search for the source of infection is essential to ensure timely and appropriate therapy.