This retrospective study was conducted to determine the risk factors for resistance to extended-spectrum cephalosporins (ESCs) and to examine the influence of previous use of an aminoglycoside with an ESC on resistance to ESCs in patients with Enterobacter bacteremia from January 1991 through December 2000. A total of 423 episodes of Enterobacter bacteremia among 414 patients were documented during the 10-year study period. Three hundred thirty-two (78%) isolates were Enterobacter cloacae, 72 (17%) Enterobacter aerogenes, and 19 (4%) other Enterobacter species. Causative isolates exhibited resistance to ESCs in 225 episodes and susceptibility in 198 episodes. Nosocomial acquisition was an independent risk factor for resistance to ESCs (odds ratio [OR], 3.4; 95% confidence interval [95%CI], 1.7-6.8). The median number of antibiotics used was significantly greater in cases caused by resistant isolates than in cases caused by susceptible isolates (OR, 1.8; 95%CI, 1.2-2.6). Resistance to ESCs was associated with previous use of any ESC (OR, 5.0; 95%CI, 2.5-10.2). The proportion of resistant episodes in patients treated previously with an aminoglycoside plus an ESC was not different from that in patients treated with an ESC alone. In conclusion, previous use of ESCs was associated with resistance to ESCs in patients with Enterobacter bacteremia; moreover, previous use of an aminoglycoside with an ESC did not significantly decrease the risk of resistance to ESCs.