A total of 250 consecutive admissions to an open-plan respiratory ICU were analyzed prospectively to identify the incidence of secondary hospital-acquired infections and possible predisposing factors. Despite preventative measures and a restricted antibiotic policy, 23.6% of patients developed secondary infections. Patients admitted after multiple trauma were the only diagnostic category of patients who showed a significantly increased incidence of secondary infections. The length of hospitalization and number of patients who had intubations or tracheostomies was higher in the group with secondary infection; the causal relationship was difficult to establish. Patients who were not intubated or tracheostomized did not develop secondary infection. Prior administration of antibiotics did not appear to influence the incidence of secondary infection. There was a significant increase in secondary infections in patients with a higher therapeutic intervention scoring system score. The predominant pathogens cultured were highly resistant Gram-negative organisms, particularly Acinetobacter sp. and Pseudomonas sp. Staphylococcus aureus was the most common Gram-positive pathogen. The ICU course was probably prolonged by the complication of nosocomial infection, which may have contributed to the deaths.