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Management of urinary tract infections is challenged by increasing antimicrobial resistance (AMR) worldwide. In this study, we describe the trends in antimicrobial resistance of uropathogens isolated from the largest private sector laboratory in Ghana over a five-year period. We reviewed positive urine cultures at the MDS Lancet Laboratories from 2017 to 2021. The proportions of uropathogens with antimicrobial resistance to oral and parenteral antimicrobials recommended by the Ghana standard treatment guidelines were determined. The proportion of multi-drug resistant isolates, ESBL and carbapenemase-producing phenotypes were determined. Of 94,134 urine specimens submitted for culture, 20,010 (22.1%) were culture positive. Enterobacterales was the most common group of organisms, E. coli (70.6%) being the most common isolate and Enterococcus spp. the most common gram-positive (1.3%) organisms. Among oral antimicrobials, the highest resistance was observed to ciprofloxacin (62.3%) and cefuroxime (60.2%) and the least resistance to fosfomycin (1.9%). The least resistance among parenteral antimicrobials was to meropenem (0.3%). The highest multi-drug resistance levels were observed among Klebsiella spp. (68.6%) and E. coli (64.0%). Extended-spectrum beta-lactamase (ESBL) positivity was highest in Klebsiella spp. (58.6%) and E. coli (50.0%). There may be a need to review the Ghana standard treatment guidelines to reflect increased resistance among uropathogens to recommended antimicrobials.