This retrospective study investigated the clinical characteristics and antimicrobial susceptibilities of 36 cases of Citrobacter freundii bacteremia treated at the Taipei Veterans General Hospital from 1996 through 1999. The results showed that the predominant infection site was the intraabdominal region and the mortality was 22%. The resistance of C. freundii to most third-generation cephalosporins and broad-spectrum penicillins increased in both nosocomial and community-acquired C. freundii bacteremia during the study period, and the strategy of using a combination of antimicrobial agents to treat C. freundii infection was effective. This study also demonstrated the importance of appropriate antimicrobial therapy to the successful outcome of C. freundii bacteremia. The guidelines of the National Nosocomial Infections Surveillance System were followed to determine trends of resistance of C. freundii to various antimicrobial agents. The resistance of C. freundii to antibiotics in 1999 (n = 10), compared with the period from 1996 through 1998 (n = 26), increased 66% for ciprofloxacin, 36% for ticarcillin/clavulanate, 70% for piperacillin/tazobactam, and 62.8% for piperacillin, but remained uniformly susceptible to imipenem/cilastatin and the new fluoroquinolone (levofloxacin). This increase in resistance was attributable to the use of third-generation cephalosporin instead of first-generation cephalosporins. These findings indicate the need for new measures to facilitate the appropriate choice of antimicrobial agents for patients with C. freundii bacteremia.