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In contrast to adults, coccidioidomycosis is a rare disease in infants and the mechanisms of disease acquisition are not well described in infants. The purpose of this study was to describe the clinical presentation, treatment, and outcome of pulmonary coccidioidomycosis in infants in an endemic area.We performed a retrospective observational study of all patients less than 12 months of age admitted to a tertiary free standing children's hospital from 2003–2012 diagnosed with coccidioidomycosis.Thirteen infants were hospitalized during the study period. The majority of the patients presented with upper and/or lower respiratory tract infection. The most common presenting symptoms included fever (77%), cough (61%), and respiratory distress (38%). Disseminated disease, included pericardial effusion, neck abscess, and lesions in the cerebellum, basal ganglia and left temporoparietal skull. Fluconazole was the initial, antifungal agent used. Amphotericin B was reserved for significant lung disease and disseminated cases. Failed response to fluconazole and amphotericin B were treated with a combination of voriconazole and caspofungin. Average length of treatment was 4 years. All patients survived to hospital discharge. The majority of the patients had resolution of chest radiograph and coccidiodal complement fixing antibody titers.Infant coccidioidomycosis has a non-specific presentation and can mimic common infant respiratory illnesses. In endemic areas, coccidioidomycosis should be considered in the differential diagnosis of infants with pulmonary symptoms unresponsive to conventional treatment. Pediatr Pulmonol. 2016;51:858–862. © 2016 Wiley Periodicals, Inc.