Background: Individuals with spinal cord injury (SCI) have a high lifelong risk for systemic infection. For optimal therapy, it is important to characterize the organisms involved in bacteremic episodes and the sites of primary infection. The increase in drug-resistant bacteria in recent years underscores the importance of gathering accurate microbiological information. Methods: We performed a retrospective study of hospitalized people with SCI using a computerized Microbiology Laboratory Database. We compared the microbiology of bacteremic episodes during initial versus unplanned subsequent hospitalizations. Data were collected on 55 bacteremic episodes in 30 people during initial hospitalization for SCI and 50 episodes in 29 people who were rehospitalized. Results: Among cases in which a site of origin could be identified, the respiratory tract was the origin of the majority of bacteremias during initial hospitalizations, and the urinary tract was the primary origin during rehospitalizations. Polymicrobial bacteremia occurred in 14 of 55 (25%) initial versus 14 of 50 (28%) subsequent hospitalization episodes. The most common pathogens were coagulase-negative staphylococci, followed by Staphylococcus aureus and Enterobacteriaceae. Bacteremia was more common in people with tetraplegia and complete neurologic lesions than in those with paraplegia and incomplete lesions. One person in the rehospitalization group died from complications of bacteremia. All others were successfully treated. Conclusions: This study describes the frequency and characteristics of bacteremia during initial and subsequent hospitalizations following SCI and examines differences in original sites of infection. This information should be considered when planning infection control measures and empiric antibiotic regimens for patients with SCI.