Background: Acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) is a rapid and ultimately fatal condition, and no effective treatment has been established. Pirfenidone has antifibrotic effects in IPF; however, its efficacy for AE-IPF is unclear. Objectives: To evaluate the efficacy of pirfenidone for AE-IPF. Methods: We retrospectively reviewed the medical records of 135 IPF patients treated during the period from April 2008 to April 2015 and identified and extracted 47 AE-IPF patients (42 men, 5 women; mean age, 73.5 years). The clinical features and outcomes of the 20 patients treated with pirfenidone were compared with those of the 27 patients treated without pirfenidone. We then excluded the 25 patients who did not receive recombinant human soluble thrombomodulin (rhTM) and analyzed data from the remaining 22 patients (20 men, 2 women; mean age, 73.7 years). Clinical features and outcomes were compared between the 10 patients treated with pirfenidone and the 12 patients who did not receive pirfenidone. Results: There were no significant differences between the two groups in baseline characteristics, except for pirfenidone use before onset. Three-month survival was significantly better in patients treated with pirfenidone than in the control group (55% vs 34%, p - 0.042). In univariate analysis, nonuse of pirfenidone was a potential risk factor for death at 3 months (hazard ratio, 6.993; p - 0.043) in patients treated with rhTM. Conclusion: A regimen of pirfenidone combined with corticosteroids and rhTM may improve survival in patients with AE-IPF. (C) 2017 Elsevier Ltd. All rights reserved.