The objectives of this study were to define the epidemiology of nosocomial bacterial colonization and infection and to define predictors of nosocomial infection among a cohort (n=423) of admissions to an acute rehabilitation unit. Overall, methicillin-resistant Staphylococcus aureus (MRSA) and enterococci were the most commonly identified colonizing organisms. Escherichia coli and Pseudomonas aeruginosa were the most commonly identified colonizing gram-negative bacilli. During 70 (16.5%) of the 423 hospitalizations in the unit, 94 nosocomial infections occurred. The most common infections were those of the urinary tract (30% of 94 infections) or a surgical site (17%), Clostridium difficile diarrhea (15%), and bloodstream infection (12.8%). Antibiotic-resistant bacteria most commonly caused bloodstream infection (41.7%) and surgical site infection (56.3%). Independent predictors of nosocomial infection at the time of admission were functional status (measured with the functional independence measure), APACHE III score, and spinal cord injury. In conclusion, gram-positive organisms were the predominant strains causing nosocomial colonization and infection. The logistic model, if verified, may be useful in defining patients who should be targeted for measures to prevent nosocomial infection.