Pseudomonas aeruginosa, a leading nosocomial pathogen, may become multidrug resistant (MDR). Its rate of occurrence, the individual risk factors among affected patients, and the clinical impact of infection are undetermined. We conducted an epidemiologic evaluation and molecular typing using pulsed-field gel electrophoresis (PFGE) of 36 isolates for 82 patients with MDR P. aeruginosa and 82 controls matched by ward, length of hospital stay, and calendar time. A matched case-control study identified individual risk factors for having MDR P. aeruginosa, and a retrospective matched-cohort study examined clinical outcomes of such infections. The 36 isolates belonged to 12 PFGE clones. Two clones dominated, with one originating in an intensive care unit (ICU). Cases and controls had similar demographic characteristics and numbers of comorbid conditions. A multivariate model identified ICU stay, being bedridden, having high invasive devices scores, and being treated with broad-spectrum cephalosporins and with aminoglycosides as significant risk factors for isolating MDR P. aeruginosa. Having a malignant disease was a protective factor (odds ratio [OR] ‫؍‬ 0.2; P ‫؍‬ 0.03). MDR P. aeruginosa was associated with severe outcomes compared to controls, including increased mortality (OR ‫؍‬ 4.4; P ‫؍‬ 0.04), hospital stay (hazard ratio, 2; P ‫؍‬ 0.001), and requirement for procedures (OR ‫؍‬ 5.4; P ‫؍‬ 0.001). The survivors functioned more poorly at discharge than the controls, and more of the survivors were discharged to rehabilitation centers or chronic care facilities. The epidemiology of MDR P. aeruginosa is complex. Critically ill patients that require intensive care and are treated with multiple antibiotic agents are at high risk. MDR P. aeruginosa infections are associated with severe adverse clinical outcomes.Pseudomonas aeruginosa is a leading cause of nosocomial infections and is responsible for 10% of all hospital-acquired infections (17, 18). Infections caused by P. aeruginosa are often severe and life threatening and are difficult to treat because of the limited susceptibility to antimicrobial agents and the high frequency of an emergence of antibiotic resistance during therapy (3, 9), thus resulting in severe adverse outcomes (4).The problem of antibiotic resistance in P. aeruginosa is on the increase (18). The heightened level of drug resistance is a result of the de novo emergence of resistance in a specific organism after exposure to antimicrobials (3) as well as of patient-to-patient spread of resistant organisms (8). Accumulation of resistance after exposure to various antibiotics and cross-resistance between agents may result in multidrug-resistant (MDR) P. aeruginosa. This condition was found primarily in patients with cystic fibrosis, where persistent infection with P. aeruginosa leads to the sequential emergence of resistance to multiple antibiotic agents. These MDR P. aeruginosa strains may be transmitted from patient to patient and sometimes lead to outbreaks among cystic fibrosis patients attending...