Pseudomonas aeruginosa is an opportunistic pathogen that causes disease in patients with impaired host defenses; it is often a cause of life-threatening nosocomial infection in critically ill and immunocompromised patients. An increase in the prevalence of multiple-drug-resistant Pseudomonas aeruginosa (MDRP) in hospitals is thus a worldwide problem. These increases are frequently related to the high selective pressure of antimicrobials commonly used in hospitalized patients, particularly extended-spectrum cephalosporins, beta-lactamase-inhibitor combinations, carbapenems, fluoroquinolones, and aminoglycosides. We evaluated the clinical and microbiological characteristics of drug-resistant P. aeruginosa and MDRP strains that were isolated at Niigata University Hospital, Japan, from 2000 to 2004. We experienced an outbreak of MDRP in 2000, but colonization only was the main feature of the outbreak. Also, the isolation rate of MDRP has decreased since 2004; this reduction in the isolation rate seems to be a result of a move to newly built ward sections in 2001 and the establishment of an infection control team (ICT) in 2003.