To identify demographics, clinical manifestations, and outcomes of patients with Coccidioides fungemia, we searched our institutional medical records to identify patients with Coccidioides fungemia treated between 1998 and 2008 and conducted a comprehensive search of the medical literature to identify previously reported cases. Coccidioides fungemia is an uncommon manifestation of coccidioidomycosis, a fungal infection caused by Coccidioides sp. endemic to the southwestern United States. Six Coccidioides fungemia patients were treated at our institution during the 10-year period. All 6 had underlying comorbid disease; three were receiving immunosuppressants. Three patients survived longer than 2 years. The literature review identified 107 patients, bringing the total cohort to 113 (mean age, 42 years). Forty-three patients (38%) had infection with the human immunodeficiency virus, 20 (18%) were receiving corticosteroids, 11 (10%) had solid organ transplants, and 5 (4%) were pregnant. Sites of extrapulmonary dissemination were reported for 97 (86%); the most common sites were liver (26/97 [27%]), spleen (21/97 [22%]), and meninges/central nervous system (17/97 [18%]). No patient showed evidence of endocarditis. At least 1 serologic test was positive in 45 (87%) of 52 patients for whom results were available. Overall mortality at 30 days was 62% (70/113; mean survival, 11.4 days). Survival was significantly worse in immunocompromised versus immunocompetent patients (22/72 [31%] vs. 19/36 [53%], respectively; P = .04). Lack of antifungal therapy predicted poor survival (8/38 [21%] vs. 32/65 [49%], respectively; P = .004). Coccidioides fungemia is an uncommon manifestation of fulminant, disseminated coccidioidomycosis. Survival is poorest in immunocompromised patients or those not receiving antifungal therapy.