A 73-year-old man was referred to our hospital in February 2009 for cough and dyspnea. A diagnosis of idiopathic pulmonary fibrosis was made on the basis of findings from chest computed tomography (CT) and a pulmonary function test (PFT). The patient was started on inhaled N-acetylcysteine in May 2009, and chest CT and PFT findings (+0.36 L; change in forced vital capacity [ΔFVC], +13.1%) had improved at 6 months. However, PFT and CT findings had worsened (-0.65 L; ΔFVC, -21%) at 17 months after starting inhaled N-acetylcysteine therapy, and pirfenidone treatment was added to inhaled NAC therapy in September 2010. CT and PFT findings (+0.47 L; ΔFVC, +19%) were markedly improved at 6 months after beginning combination therapy and remained at 36 months. This is the first report of successful treatment for disease progression of idiopathic pulmonary fibrosis with combination therapy comprising N-acetylcysteine and pirfenidone.