We determined the prevalence and spread of antibiotic resistance and the characteristics of ESBL producing and/or multi drug resistant (MDR) Escherichia coli isolates collected from urine samples from urology services in the Euregio Meuse-Rhine, the border region of the Netherlands (n=176), Belgium (n=126) and Germany (n=119). Significant differences in resistance between the three regions were observed. Amoxicillin-clavulanic acid resistance ranged from 24% in the Netherlands to 39% in Belgium (p=0.018), from 20% to 40% (p<0.004) for the fluoroquinolones and from 20% to 40% (p=0.018) for the folate antagonists. Resistance to nitrofurantoin was less than 5%. The prevalence of ESBL producing isolates varied from 2% among the Dutch isolates to 8% among the German ones (p=0.012) and were mainly CTX-M 15. The prevalence of MDR isolates among the Dutch, German and Belgian isolates was 11%, 17% and 27%, respectively (p< =0.001 for the Belgian compared with the Dutch isolates). The majority of the MDR and ESBL producing isolates belonged to ST131. This study indicates that most antibiotics used as first choice oral empiric treatment for UTIs (amoxicillin-clavulanic acid, fluoroquinolones and folate antagonists) are not appropriate for this purpose and that MDR strains such as CTX-M producing ST131 have spread in the entire Euregion. Our data stress the importance of ward specific surveillance to optimize empiric treatment. Also, prudent use of antibiotics and further research to alternative agents are warranted.