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This retrospective cohort study evaluated characteristics, treatment patterns, and clinical outcomes in adults with locally advanced/metastatic urothelial carcinoma (la/mUC) receiving first-line (1L) systemic treatment with or without avelumab 1L maintenance (1LM) between January 2020 and July 2023. The index date was the first date with a claim for 1L systemic therapy after a la/mUC diagnosis. Patients with continuous health plan enrollment for ≥6 months before and ≥1 month after the index date were identified from Carelon Research's Healthcare Integrated Research Database. Of 2820 patients receiving 1L treatment, 37.0% received platinum-based chemotherapy (PBC); 39.0%, immuno-oncology (IO) monotherapy; and 24.0%, other therapies. Renal disease and other comorbidities influenced 1L regimen choice. Healthcare resource utilization (HCRU) and costs were reported for patients receiving second-line (2L) treatment. HCRU was high in 32.8% of patients (926 of 2820) who received 2L treatment. Median all-cause direct medical costs per patient per month were USD 15,859, USD 19,781, USD 11,346, and USD 9516 for 1L PBC, 1L PBC + avelumab 1LM, 1L IO monotherapy, and 1L other therapies, respectively. Most direct healthcare costs were attributed to all-cause outpatient visits.