Introduction Limited data are available in the United States on the 12-month epidemiology, outpatient (OP) antibiotic treatment patterns, outcomes, and costs associated with complicated urinary tract infections (cUTIs) in adult patients. Methods A retrospective observational cohort study of adult patients with incident cUTIs in IBM® MarketScan® Databases between 2017-2019 was performed. Patients were categorized as OP or inpatient (IP) based on initial setting of care for index cUTI and were stratified by age (<65 years vs ≥65 years). OP antibiotic treatment patterns, outcomes, and costs associated with cUTIs among adult patients over a 12-month follow-up period were examined. Results During study period, 95,322 patients met inclusion criteria. Most patients were OPs (84%) and aged <65 years (87%). Treatment failure (receipt of new unique OP antibiotic or cUTI-related ED visit/IP admission) occurred in 23% and 34% of OPs aged <65 years and ≥ 65 years, respectively. Treatment failure was observed in over 38% of IPs, irrespective of age. Across both cohorts and age strata, >78% received ≥2 unique OP antibiotics, >34% received ≥4 unique OP antibiotics, >16% received repeat OP antibiotics, and >23% received ≥1 intravenous (IV) OP antibiotic. The mean 12-month cUTI-related total healthcare costs were $4,697 for OPs <65 years, $8,924 for OPs >65 years, $15,401 for IPs <65 years, and $17,431 for IPs ≥ 65 years. Conclusion These findings highlight the substantial 12-month healthcare burden associated with cUTIs and underscore the need for new outpatient treatment approaches that reduce the persistent or recurrent nature of many cUTIs.