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Abstract: Objectives: Tracheo-innominate artery fistula (TIF) is a rare but life-threatening complication of tracheostomy. There are many reports about TIF but the mechanism of TIF formation remains poorly documented. Our objective is to investigate the TIF pathologically and suggest the possible mechanism of TIF formation. Patient and Methods: The patient was an 11-year old boy with a history of severe childhood epilepsy, cerebral palsy, and psychomotor retardation who died from TIF. We investigated the TIF histopathologically through his autopsy and reviewed bibliographical considerations. Results: Autopsy revealed massive blood aspiration from a large TIF and histopathological findings showed the following: (1) fibroepithelial polyps around the fistula; (2) squamous metaplasia of tracheal mucosa; (3) disappearance of tracheal cartilages and tracheal glands; and (4) arteritis (infiltration of neutrophils into the mesarterium and endarterium). Probably, (1) and (2) indicate chronic and repetitive irritations caused by cannula. (3) and (4) indicate intense inflammation caused by local infection. In this case, it is suggested that the chronic damage by cannula and the local infection resulted in the fistula formation and rupture of innominate artery. Conclusion: The present case suggests a pathogenesis in which chronic damage to the anterior tracheal wall by the cannula and consequent infection led to fistulation and rupture of the innominate artery. [Copyright &y& Elsevier]