BACKGROUND: Escherichia coli is the leading cause of urinary tract infections (UTI). Current Infectious Diseases Society of America (IDSA) guidelines recommend the use of fluoroquinolones when resistance to trimethoprim-sulfamethoxazole is greater than 10% to 20%. Identification of risk factors for fluoroquinolone-resistant E. coli may provide information to help in choosing the optimal empiric treatment of patients with UTI. OBJECTIVE: To identify risk factors for fluoroquinolone-resistant E. coli in patients with UTI. METHODS: Retrospective case control study of UTI caused by quinolone-resistant E. coli. RESULTS: Risk factors for fluoroquinolone-resistant E. coli UTI included recurrent UTI (odds ratio [OR], 2.28; P = 0.017), underlying medical disease (OR, 5.28; P < 0.001), urinary tract abnormalities (OR, 2.99; P = 0.002), prior hospitalization within the last 6 months (OR, 5.58; P = 0.032) and prior treatment with antibiotics within the last 6 months (OR, 13.72; P < 0.001). Isolates were susceptible to nitrofurantoin (94.9%), cepholosporins (79.7%), aminoglycosides (amikacin 97.5%, gentamicin 75.9%), and imipenem (98.7%). CONCLUSIONS: Fluoroquinolones should be used with caution in patients with UTI and risk factors for fluoroquinolone-resistant E. coli. © 2009 Lippincott Williams & Wilkins, Inc.