Objectives: To determine the overall in vitro resistant rates among common uropathogens in order to indicate alternative antimicrobials for consideration in the future treatment of urinary tract infection (UTI). Materials and methods: Data included in this study were derived from 4 years (2013-2016) cross-sectional, a retrospective study carried out in Aseer Central Hospital, Saudi Arabia. Culture positives urine and other UT specimens (n=47193) obtained from patients suspected of having UTIs were identified and tested for antimicrobial assay using the VITEK 2 system. The analysis was done using SPSS software on culture positive samples against 39 antimicrobial agents and combinations of more than one agent. Results: Of the 47193 culture positive uropathogens, 51.5% were resistant to the 39 agents, whereas 48.5% were sensitive (p=0.7969). Antimicrobials with high sensitivity to all uropathogens were linezolid (99.1%), daptomycin (98.3%), vancomycin (86.7%), ertapenem (86.3%), teicoplanin (85.5%), tigecycline (85.3%), imipenem (82.4%), meropenem (79.6%), piperacillin/tazobactam (78.6%), and colistin (76.2%). In contrast, antimicrobials with high resistance were cephalothin (91.0%), nalidixic acid (86.7%), cefuroxime (79.6%), cefazolin (76.3%), mezlocillin (76.1%), piperacillin (73.6%), ceftriaxone (72.9%), norfloxacin (72.8%), ciprofloxacin (71.7%), and cefotaxime (69.7%). Conclusions: Empirically prescribed antimicrobials have displayed remarkable resistance in this survey. Information on the local antimicrobial trends is needed to plan evidence-based recommendations. Drugs such as linezolid, daptomycin, vancomycin, ertapenem, teicoplanin and tigecycline indicated good alternatives (≥ 85% sensitivity) for consideration in empirical UTI therapy. However, cephalothin, nalidixic acid, and cefuroxime revealed high resistance rates (≥ 80%).