Urinary tract infections (UTIs) are among the most common bacterial infections, with uropathogenic Escherichia coli (UPEC) as the main etiologic agent of uncomplicated UTIs (uUTIs). The prevalence of uUTis caused by organisms with antimicrobial resistance (AMR) is increasing worldwide, complexifying the disease management and increasing the risk of complications. In efforts to develop new strategies for uUTI prevention, it is imperative to understand factors associated with the occurrence of new episodes. This retrospective cohort study aimed to assess the incidence of uUTIs caused by UPEC (UPEC-uUTIs) or unknown etiology (untested uUTIs) in adults aged ≥18 years receiving care in a San Francisco healthcare system. During 2014-2019, 1087 UPEC-uUTI and 4106 untested uUTI cases were documented, of which 324 (29.8%; 95% confidence interval: 27.1%-32.6%) and 1030 (25.1%; 95% confidence interval: 23.8%-26.4%) were followed by ≥1 new episode of uUTI within 12 months. In the UPEC-uUTI cohort, male gender, diagnosis of diabetes mellitus, and prior uUTI were risk factors for new episodes of uUTI. At the time of first UPEC-uUTI diagnosis, antimicrobial prescriptions were retrieved for 41.1% of cases. When tested, AMR was most frequently reported for trimethoprim/sulfamethoxazole or trimethoprim/sulfamethoxazole prescribed with other antimicrobials. Our study provides important information on the incidence and risk of repeated episodes of uUTIs, as well as on AMR related to them.