OBJECTIVE: To describe the epidemiology of endemic multidrug-resistant Pseudomonas aeruginosa colonizations and infections in critically ill patients. DESIGN: Prospective study on bacterial strain typing and retrospective cohort study of charts of patients in the intensive care unit (ICU). PATIENTS: Fifty-three patients with P aeruginosa isolated from clinical cultures in 2001 were selected, divided into those with P aeruginosa in vitro resistant to at least two classes of antibiotics (multidrug-resistant, n = 18) and those susceptible to all or resistant to only one antibiotic (susceptible, n = 35). RESULTS: Risk factors for multidrug-resistant P aeruginosa included maxillary sinusitis, long-dwelling central venous catheters, prolonged use of certain antibiotics, a high lung injury score, and prolonged mechanical ventilation and duration of stay. The frequency of colonization (approximately 50%) versus infection (ie, ventilator-associated pneumonia) did not differ between the groups. On amplified fragment-length polymorphism analysis, 64% of the multidrug-resistant strains had been potentially transmitted via cross-colonization and 36% bad probably originated endogenously. ICU mortality was 22% in the multidrug-resistant group and 23% in the susceptible group, although the duration of mechanical ventilation was longer in the former. CONCLUSIONS: Patients with sinusitis who stayed in the ICU longer, were ventilated longer because of acute lung injury, received antibiotics for longer durations, and bad long-dwelling central venous catheters ran an elevated risk of acquiring multidrug-resistant P aeruginosa. These patients did not have a higher mortality than patients with susceptible P aeruginosa. Prevention of the emergence of multidrug-resistant strains requires changes in infection control measures and antibiotic policies in our ICU.