Diffuse alveolar hemorrhage (DAH) is a rare disease characterized by dyspnea, cough, hemoptysis, and new alveolar infiltrates. Among the various underlying disorders, vasculitis is believed to play a significant role in the pathogenesis of DAH. Here we report the first case of a patient with Down syndrome who developed DAH secondary to anti-neutrophil cytoplasmic antibody-associated vasculitis. This case highlights the significance of vasculitis as well as pulmonary hypoplasia and vulnerability associated with Down syndrome in the development of DAH.