The present study was conducted to identify risk factors for ciprofloxacin resistance in bloodstream infections due to extended-spectrum beta -lactamase-producing Escherichia coli and Klebsiella pneumoniae (ESBL-EK). ESBL production was determined in stored E. coli and K. pneumoniae blood isolates from January, 1998, to December, 2002, by National Committee for Clinical Laboratory Standards (NCCLS) guidelines and/or double-disk synergy test. Antimicrobial susceptibility was determined by the disk diffusion test method. A total of 133 patients with ESBL-EK bacteremia were analyzed retrospectively. A total of 80 (60.2%) patients experienced bacteremia due to strains resistant to ciprofloxacin. There were no significant differences in age, sex, and APACHE II score between the ciprofloxacin-resistant group (CIP-R) and-susceptible group (CIPS). The most common primary site of infection in CIP-R was pancreaticobiliary tract infection (46/80, 57.5%) and that in CIP-S was unknown primary site (23/53, 43.4%). Independent risk factors for ciprofloxacin resistance were: prior use of fluoroquinolones (OR, 5.53; 95% CI, 1.56-25.42, p = 0.032), indwelling urinary catheter (OR, 3.68; 95% CI, 1.27-10.67, p = 0.017), and invasive procedure within 72 hr prior to bacteremia (OR, 4.03; 95% CI, 1.44-11.25, p = 0.008). Our data suggest that strategies designed to reduce the ciprofloxacin resistance rate in ESBL-EK strains should focus on limiting the use of fluoroquinolones and minimizing invasive procedures, including insertion of a urinary catheter.