INTRODUCTION: The aim of this study was to determine incidence, risk factors, and impact on outcome of intensive care unit (ICU)-acquired Stenotrophomonas maltophilia. METHODS: This prospective observational case-control study, which was a part of a cohort study, was conducted in a 30-bed ICU during a three year period. All immunocompetent patients hospitalised >48 hours were eligible. Patients with non-fermenting Gram-negative bacilli (NF-GNB) at ICU admission were excluded. Patients without ICU-acquired S. maltophilia who developed an ICU-acquired NF-GNB other than S. maltophilia were also excluded. Screening (tracheal aspirate and skin, anal, and nasal swabs) for NF-GNB was performed in all patients at ICU admission and weekly. Univariate and multivariate analyses were performed to determine risk factors for ICU-acquired S. maltophilia and for ICU mortality. RESULTS: Thirty-eight (2%) patients developed an S. maltophilia ICU-acquired colonisation and/or infection and were all successfully matched with 76 controls. Chronic obstructive pulmonary disease (COPD) and duration of antibiotic treatment (odds ratio [OR] [95% confidence interval (CI)] = 9.4 [3 to 29], p < 0.001, and 1.4 [1 to 2.3], p = 0.001, respectively) were independently associated with ICU-acquired S. maltophilia. Mortality rate (60% versus 40%, OR [95% CI] = 1.3 [1 to 1.7, p = 0.037]), duration of mechanical ventilation (23 +/- 16 versus 7 +/- 11 days, p < 0.001), and duration of ICU stay (29 +/- 21 versus 15 +/- 17 days, p < 0.001) were significantly higher in cases than in controls. In addition, ICU-acquired infection related to S. maltophilia was independently associated with ICU mortality (OR [95% CI] = 2.8 [1 to 7.7], p = 0.044). CONCLUSION: COPD and duration of antibiotic treatment are independent risk factors for ICU-acquired S. maltophilia. ICU-acquired S. maltophilia is associated with increased morbidity and mortality rates. ICU-acquired infection related to S. maltophilia is an independent risk factor for ICU mortality.