Despite significant advances in burn care, infection remains a major cause of morbidity and mortality in burn patients. We sought to determine accurate infection rates, risk factors for infection, and the percentage of infections caused by resistant organisms. In addition, we attempted to identify interventions to decrease the use of antimicrobial drugs. Data were collected prospectively from 157 burn patients admitted to the University of Iowa Carver College of Medicine burn treatment center from October 2001 to October 2002. A research assistant reviewed the medical record for each patient identified by burn surgeons as being infected to determine whether these episodes met the infection control criteria for nosocomial infections. The infection control assessment agreed with the surgeon's assessment for 16.7% of the pneumonias, 70.0% of the burn wound infections, 57.1% of the urinary tract infections, and 70.0% of the bloodstream infections. By multiple logistic regression analysis, body surface area burned, comorbidities, and use of invasive devices were significantly related to acquisition of nosocomial infections as identified by both the burn surgeons and the infection control criteria. Staphylococcus aureus and Pseudomonas were the most common resistant organisms identified. In our population, surgeons could decrease antimicrobial use by using explicit criteria for identifying patients with hospital-acquired infections, limiting perioperative prophylaxis to patients at highest risk of infection, and decreasing the incidence of nosocomial infection with reduced use of devices and strict adherence to aseptic technique.