We report a case of fatal pulmonary infection caused by Mycobacterium abscessus in a middle-aged patient with acquired esophago-pulmonary fistula which contributed to repeated exacerbation. Acquired benign esophago-pulmonary fistula is uncommon. After a 55-year-old woman was diagnosed with pulmonary Mycobacterium avium disease in 1989 and improved with multidrug chemotherapy, she developed pulmonary M. abscessus in 2001. Despite multi-drug treatment, she suffered repeated exacerbation and her condition gradually deteriorated. Chest computed tomography (CT) showed esophago-pulmonary fistula which was comfermed by esophagoscopy. An M. abscess infection may give rise to adhesions between the tracheobronchial lymph nodes and the neighboring esophagus, with subsequent development of a traction diverticulum which may extend to the tracheobronchial tree. In the present case, aspiration of liquids through the fistula induced a cough reflex, and M. abscessus spread through the airway. It might be possible that esophago-pulmonary fistula is not only a complication of pulmonary M. abscessus infection but also an exacerbation factor.