BACKGROUND. Multidrug-resistant (MDR) Acinetobacter baumannii and Pseudomonas aeruginosa have emerged as the causes of nosocomial infections in critically ill patients. OBJECTIVE. To characterize the incidence of these MDR bacteria over time in the military healthcare system, comparing isolates recovered from overseas combat casualties with isolates recovered from local military and civilian patients. METHODS. Retrospective electronic records review of culture and/or susceptibility testing results of patients admitted to a military level I trauma center in San Antonio, Texas, during the period from January 2001 through December 2008. Multidrug resistance was defined as the first isolated organism resistant to 3 or more classes of antimicrobial agents. RESULTS. Over time, the percentage of MDR A. baumannii isolates increased from 4% to 55%, whereas the percentage of MDR P. aeruginosa isolates increased from 2% to 8%. Respiratory tract specimens had a higher percentage of MDR A. baumannii isolates (49%), compared with specimens obtained from blood (30%), wound sites (24%), or urine (19%). No difference in the percentages of MDR P. aeruginosa isolates was observed with regard to source of specimen. The percentage of MDR A. baumannii isolates recovered was higher among patients who had been deployed overseas (52%) than among local patients (20%). When isolates recovered from patients in the burn intensive care unit (53% of MDR A. baumannii isolates) were removed from analysis, the percentage of MDR A. baumannii isolates decreased from 38% to 30% while the percentage of MDR P. aeruginosa isolates remained unaffected. CONCLUSION. The percentage of MDR A. baumannii isolates increased in this facility among combat casualties and among local patients, which indicates nosocomial transmission; however, there was no significant increase in the percentage of MDR P. aeruginosa isolates. Isolated changes in the MDR pathogens within a facility can occur. Possible interventions to limit the spread of these organisms could include implementing aggressive infection control practices, controlling antibiotic use, and using active culture surveillance.