OBJECTIVES: This study aims to describe baseline characteristics, antifungal treatment patterns, healthcare utilization, costs, and mortality in patients with central nervous system (CNS) and non-CNS disseminated coccidioidomycosis. METHODS: A retrospective study using IQVIA claims data was conducted to identify adults with disseminated coccidioidomycosis in two mutually exclusive cohorts: those with CNS and those with non-CNS disease. Patients had to have ≥1 medical claim for disseminated coccidioidomycosis from October 2015 to November 2022. Antifungal treatment patterns were assessed, as were all-cause healthcare utilization, costs, and mortality during follow-up. RESULTS: In total, 2218 patients were identified, 28.2% (626/2218) with CNS and 71.8% (1592/2218) with non-CNS disease. In both cohorts, 70.9% (444/626) and 71.6% (1140/1592) of patients initiated first-line antifungal treatment, most with fluconazole (881/1140, 77.3% to 372/444, 83.8%), followed by an azole + lipid amphotericin B (21/444, 4.7% to 81/1140, 7.1%). Azole monotherapy was used often over subsequent lines of antifungal treatment in both cohorts (1049/1140, 92.0% to 122/129, 94.6%). Polyenes peaked in the latter lines of therapy (24/182, 13.2% to 79/408, 19.4%), mostly administered with azoles. Median baseline costs in the CNS and non-CNS cohorts were substantial (122 and 242, respectively). After diagnosis, 29.7% (186/626) of patients in the CNS cohort experienced a subsequent hospitalization and all-cause cost of 8 664 per person per year. The non-CNS patients experienced a similar proportion of patients requiring hospitalization (469/1592, 29.5%) and all-cause costs of 1 240 per person per year. Between 5.4% (34/626) and 6.7% (106/1592) of patients died during follow-up, with death more likely in those with concomitant pulmonary coccidioidomycosis, sepsis, certain immunosuppressive diseases, and prior azole use. DISCUSSION: Most patients with either CNS or non-CNS disseminated coccidioidomycosis received an azole first line and demonstrated azole-cycling over subsequent lines. Polyenes were used in the latter lines. Patients utilized substantial healthcare resources and accrued appreciable costs, both before and after diagnosis.