Quinolone-resistant Escherichia coli (QREC) strains are being isolated with increasing frequency. From 1993 to 1998, 40 cases of QREC bacteremia were observed in a teaching hospital; 25 episodes (63.5%) were community-acquired. The incidence of QREC bacteremia increased steadily, from 6.7% to 24.6% during 5 years, and correlated with the significantly increased use of fluoroquinolones (P = .003, r = 0.98). When the 40 QREC bacteremic patients were compared with 80 patients with bacteremia due to quinolone-susceptible E. coli, prior fluoroquinolone use was the only independent risk factor for QREC bacteremia (P = .001). A high APACHE II score was the only independent risk factor for death. The rate of multidrug resistance of QREC was much higher (60%) than that of quinolone-susceptible isolates (13.8%). Pulsed-field gel electrophoresis patterns of these isolates were diverse. Therefore, the isolates revealed little evidence of clonal spread and may have emerged in direct response to the selective pressure exerted by prior fluoroquinolone use.