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Background/Objectives: We aimed to assess the prevalence and risk factors for acquisition of extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli (E. coli) in children admitted with urinary tract infection (UTI) at a tertiary university hospital in Saudi Arabia, as well as to investigate antibiotic resistance patterns. Methods: This retrospective cross-sectional study involved hospitalized children aged 0–14 years from January 2018 to December 2022 with urine cultures that grew E. coli or ESBL-producing E. coli. Data of the antimicrobial susceptibility for isolated bacteria were collected. Results: This study analyzed 242 urine samples obtained from 119 children with E. coli UTIs. Of these, 20.7% (n = 50) were ESBL producers. Previous antibiotic use (last 3 months), prophylactic antibiotic use, prior UTI (last 3 months), recurrent UTIs, and underlying co-morbidities (p = 0.011, <0.001, 0.025, <0.001, and 0.013, respectively) had a significant relationship with increased risk of ESBL E. coli UTIs. Generally, the highest resistance rates in the ESBL-producing isolates were for ampicillin and third-generation cephalosporin. Conversely, all ESBL-positive isolates were sensitive to meropenem, with variable resistance rates to other antibiotics as amikacin, nitrofurantoin, quinolones and trimethoprim/sulfamethoxazole (2%, 8%, 56% and 64%, respectively). Conclusions: There is a high prevalence of ESBL production among children hospitalized with E. coli UTIs. Addressing ESBL UTI risk factors helps to recognize high-risk cases and enhance proper antibiotic use. [ABSTRACT FROM AUTHOR]