Enterobacter cloacae is an important nosocomial pathogen. However, few studies specifically dealing with the clinical characteristics and outcome of extended-spectrum beta-lactamase (ESBL)-producing E. cloacae infections have been published. During an 8-year period in a medical center, of 610 E. cloacae bacteremic isolates, 138 (22.6%) with ESBL genes were designated the ESBL group, and 120 (19.6%) cefotaxime-nonsusceptible isolates without the ESBL phenotype and genes were designated the control group. Of the former group of isolates, 133 (96.3%) carried the bla(SHV-12) gene, 3 (2.1%) had bla(CTX-M3), and 2 (1.4%) had both the bla(SHV-12) and bla(CTX-M3) genes. After patients under the age of 18 years were excluded, there were 206 adults with E. cloacae bacteremia, and these consisted of 121 patients in the ESBL group and 85 in the control group. More episodes of hospital-onset and polymicrobial bacteremia, increased severity of illness, more cases of bacteremia onset in intensive care units (ICUs), and longer stays in the hospital and ICU after bacteremia onset were noted in the ESBL group. However, the crude and sepsis-related mortality rates in two groups were similar. Of the ESBL group, the in-hospital sepsis-related mortality rate of patients definitively treated by a carbapenem was lower than that of those treated by noncarbapenem beta-lactams (5/53, or 9.4%, versus 13/44, or 29.5%; P = 0.01) though the difference was not significant in the hierarchical multivariate analysis (P = 0.46). Among 62 patients with follow-up blood cultures within 14 days of bacteremia onset, breakthrough bacteremia was more common in those treated by a noncarbapenem beta-lactam agent than in those treated by a carbapenem (18/31, or 58.0%, versus 3/31, or 9.6%; P < 0.001). Thus, carbapenem therapy for ESBL-producing E. cloacae that cause bacteremia may provide therapeutic benefits.