Quinolone-resistant (QR) Escherichia coli may have lower invasive capacity than does quinolone-susceptible E. coli. To evaluate this, we prospectively collected data regarding all cases of E. coli invasive urinary tract infections (IUTI) in 669 adults admitted to the Infectious Diseases Unit of our hospital during a 3-year period, as well as 10,950 patients with cystitis or asymptomatic bacteriuria who presented to the outpatient clinic during a 1-year period. QR E. coli was isolated in 20% of patients with cystitis, compared with 8% of those with IUTI (P< .05). The proportion of E. coli isolates that were quinolone resistant was similar in patients with bacteremic and nonbacteremic IUTI. The factors of urinary manipulation and structural abnormalities were independently associated with the presence of quinolone resistance. Old age was the only variable independently associated with blood invasion. QR E. coli is less likely to produce invasive disease (pyelonephritis and prostatitis) than is quinolone-susceptible E. coli. However, once pyelonephritis or prostatitis have developed, there is no difference in the incidence of bacteremia. © the Infectious Diseases Society of America 2001.