OBJECTIVE: Urinary tract infections (UTIs) are among the most common ailments encountered in primary care practice. Up to 50% of all women report having had a UTI during their lifetime. Several national treatment guidelines recommend a fluoroquinolone first-line for UTI in areas where Escherichia coli resistance to trimethoprim-sulfamethoxazole (TMP/SMX) is >10-20%. The current study developed a model to assess the economic impact of using ciprofloxacin, a fluoroquinolone, first-line in an area with high levels of E. coli TMP/SMX resistance. METHODS: The economic model utilized a treatment algorithm from an IPA in southern California where the reported TMP/SMX resistance rate was 38%. The IPA's standard treatment algorithm for uncomplicated UTIs, which was incorporated into the model, included an initial office visit, dipstick urine, culture and sensitivity, and prescription. If failure occurred, a second office visit and prescription were incorporated into the model. The model's clinical parameters included the local E. coli resistance rates to TMP/SMX (38%) and to ciprofloxacin (4%) and estimates of failure to the prescribed antimicrobial (42%). Medicare reimbursement rates for office visits and laboratory costs, and drug costs of $1.62 for TMP/SMX (800/160 mg bid x 3 days) and $10.43 for ciprofloxacin (250 mg bid x 3 days), based on maximum allowable cost, were used. RESULTS: The total average treatment cost at the IPA was $91.52 for a TMP/SMX-treated patient vs. $84.06 for a ciprofloxacin-treated patient. Resistance rates and failure were the most significant factors in driving treatment costs. CONCLUSIONS: While cost of drug therapy is a factor in antimicrobial selection, local resistance rates, failure rates and the impact of total treatment cost should be considered when developing treatment algorithms for UTI. Extended recovery time and lost productivity are implications of failure that may impact patient satisfaction with the health plan and should be assessed in future studies.