Coccidioidomycosis is a fungal infection endemic to the southwestern United States. Musculoskeletal involvement is rare, and there are few reports with clear recommendations regarding treatment. The purpose of this study was to review a series of 25 patients with musculoskeletal coccidioidomycosis and to assess their outcomes with respect to presentation and treatment. There were 36 lesions among the 25 patients, 8 located in the spine, with the remainder distributed throughout the body. Seventeen patients had a delay in diagnosis of more than 1 month. Eight patients had an elevated white blood cell count, and 10 had an elevated sedimentation rate. Only 7 of the patients had an overt pneumonia before the musculoskeletal presentation. Twenty-four patients underwent formal irrigation and debridement and 22 patients had at least 1 course of Amphotericin B. The average followup after the initiation of treatment was 3.5 years, ranging from 2 to 10 years. Seven patients had recurrent lesions that required further surgical intervention, 4 of whom had a delay in diagnosis of more than 1 month. There were 3 deaths. All surviving patients were free of disease at final followup.