Because of increasing antibiotic resistance in Escherichia coli, the main uropathogen of uncomplicated urinary tract infections (UTIs), updated susceptibility data are vital in guiding the selection of first-line treatment agents. interpretation of these data depends on the breakpoints adopted, that may vary among different guidelines.In this study we report the minimum inhibitory concentrations (MICs) of eight antibiotics and compare antimicrobial susceptibility results obtained in 2315 E. coli strains recently collected during the ARESC survey using EUCAST and CLSI breakpoints. We have also evaluated the clinical impact of breakpoint discrepancies on the overall susceptibility patterns.Fosfomycin, nitrofurantoin and mecillinam showed the highest susceptibility rates in all countries (>92%) according to both CLSI and EUCAST criteria. Minor category shifts were observed for ciprofloxacin, amoxicillin-clavulanic acid, ampicillin and trimethoprim/sulfamethoxazole. A large number of strains classified as intermediate resistant to cefuroxime according to CLSI are included by the EUCAST in the susceptible category.In conclusion, fosfomycin, mecillinam, and nitrofurantoin have preserved their in vitro activity in all countries investigated, regardless of the criteria adopted. They continue to represent effective options for the empiric therapy of female patients with uncomplicated cystitis. The use of different interpretative criteria for E. coli responsible for UTIs therefore has no influence on the decision to be taken by the physicians managing the patients.