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Objective: To estimate the prevalence of ventilator-associated pneumonia caused by Pseudomonas aeruginosa in patients at risk for ventilator-associated pneumonia and to describe risk factors for P. aeruginosa ventilator-associated pneumonia., Design: Prospective, observational study., Setting: ICUs at 56 sites in 11 countries across four regions: the United States (n = 502 patients), Europe (n = 495), Latin America (n = 500), and Asia Pacific (n = 376)., Patients: Adults intubated and mechanically ventilated for 48 hours to 7 days, inclusive., Interventions: None (local standard of care)., Measurements and Main Results: Ventilator-associated pneumonia prevalence as defined by local investigators were 15.6% (293/1,873) globally, 13.5% in the United States, 19.4% in Europe, 13.8% in Latin America, and 16.0% in Asia Pacific (p = 0.04). Corresponding P. aeruginosa ventilator-associated pneumonia prevalences were 4.1%, 3.4%, 4.8%, 4.6%, and 3.2% (p = 0.49). Of 50 patients with P. aeruginosa ventilator-associated pneumonia who underwent surveillance testing, 19 (38%) had prior P. aeruginosa colonization and 31 (62%) did not (odds ratio, 7.99; 95% CI, 4.31-14.71). Of predefined risk factors for multidrug resistance (hereafter, risk factors), the most frequent in all patients were antimicrobial therapy within 90 days (51.9% of enrolled patients) and current hospitalization of more than or equal to 5 days (45.3%). None of these risk factors were significantly associated with P. aeruginosa ventilator-associated pneumonia by multivariate logistic regression. Risk factors associated with prior P. aeruginosa colonization were antimicrobial therapy within 90 days (odds ratio, 0.46; 95% CI, 0.29-0.73) and high proportion of antibiotic resistance in the community or hospital unit (odds ratio, 1.79; 95% CI, 1.14-2.82)., Conclusions: Our findings suggest that ventilator-associated pneumonia remains a common ICU infection and that P. aeruginosa is one of the most common causative pathogens. The odds of developing P. aeruginosa ventilator-associated pneumonia were eight times higher in patients with prior P. aeruginosa colonization than in uncolonized patients, which in turn was associated with local resistance.