ABSTRACT: INTRODUCTION: To investigate the relationship between Pseudomonas aeruginosa acquisition on the intensive care unit (ICU), environmental contamination and antibiotic selective pressure against P. aeruginosa. METHODS: An open, prospective cohort study was carried out in a 16-bed medical ICU where P. aeruginosa was endemic. Over a 6-month period, all patients without P. aeruginosa on admission and with a length of stay >72 h were included. Throat, nasal, rectal, sputum and urine samples were taken on admission and at weekly intervals and screened for P. aeruginosa. All antibiotic treatments were recorded daily. Environmental analysis included weekly tap water specimen culture and presence of other patients colonized with P. aeruginosa. RESULTS: One-hundred and twenty-six patients were included, comprising 1345 patient-days. Antibiotics were given to 106 patients (antibiotic selective pressure for P. aeruginosa in 39). P. aeruginosa was acquired by 20 patients (16%) and was isolated from 164/536 environmental samples (31%). Two conditions were independently associated with P. aeruginosa acquisition by multivariate analysis: (i) patients receiving [greater than or equal to]3 days of antibiotic selective pressure together with at least one colonized patient on the same ward on the previous day (OR=10.3 [95%CI: 1.8-57.4]; P=0.01); and (ii) presence of an invasive device (OR=7.7 [95%CI: 2.3-25.7]; P=0.001). CONCLUSIONS: Specific interaction between both patient colonization pressure and selective antibiotic pressure is the most relevant factor for P. aeruginosa acquisition on an ICU. This suggests that combined efforts are needed against both factors to decrease colonization with P. aeruginosa.