This study aimed to establish the pattern of the antimicrobial resistance among the leading uropathogens causing community-acquired UTIs in an area of the region of Apulia, Southern Italy. Twenty-one thousand and two hundred outpatients, 6,893 males and 14,307 females, were enrolled. Urinary isolates were identified by conventional methods and the susceptibility to 18 antimicrobials determined. Recognized uropathogens Escherichia coli, Klebsiella pneumoniae and Proteus mirabilis were isolated from 3175 positive samples, E. coli accounting for 68.04% of positive cultures. Most overall resistance was to ampicillin, while the resistance rate to cephalothin was higher than that of third generation cephalosporins. Although to a different degree, all the bacteria had an overall good susceptibility rate to quinolones as well as to fosfomycin but increased resistance to sulfamethoxazole/trimethoprim. Our results confirm that E. coli is the leading uropathogen and provide information about the antimicrobial susceptibility patterns of the main pathogens causing community-acquired UTIs. These findings should be taken into account to help maintain the safety and efficacy of treatment for community-acquired UTIs.