OBJECTIVE Mediastinal lymph node (MLN) enlargement detected on chest computed tomography (CT) is frequent in patients with interstitial lung disease (ILD) and is shown in approximately 70% of cases of idiopathic pulmonary fibrosis (IPF). We hypothesized that enlarged MLNs might be a predictor of poor prognosis, associated with lower survival and stronger disease severity. METHODS This study included patients with idiopathic pulmonary fibrosis (IPF) or nonspecific interstitial pneumonia (NSIP) from January 2009 to December 2018. Baseline chest CT scan and one-year follow-up scan of the patients were reviewed for the extent of lung fibrosis and MLNs. Two radiologists independently assessed MLN diameter and location. Patients with drug toxicity-related ILD, sarcoidosis, chronic hypersensitivity pneumonitis and other rare idiopathic interstitial pneumonias were excluded. The primary endpoint was survival. Secondary endpoints included number of hospitalizations for respiratory causes, lung function evaluated by forced vital capacity (FVC) and diffusing capacity for carbon monoxide (DLCO), and lung fibrosis score determined by CT scan. RESULTS We retrospectively reviewed the medical registries of 110 patients with chronic pulmonary fibrosis (mean age 71 years, 60.4% male). Nine participants were excluded because the CT scans were of poor diagnostic quality for the evaluation of the mediastinum or unavailable for review. The analysis of 101 patients showed that enlarged MLNs (short axis diameter ≥10 mm) were present in 50.5% (n=51) and strongly predicted survival (HR= 2.11, 95% CI 1.12-3.96, p = 0.020). Patients with MLN enlargement experienced greater number of hospitalizations for respiratory causes (mean 2.5 vs. 1.8, p = 0.010) and had significantly worse lung function parameters (FVC, 71% vs. 81%, p = 0.018 and DLCO, 40% vs. 50%, p = 0.001) and a higher lung fibrosis score (50% vs. 39%, p = 0.001). CONCLUSIONS In patients with IPF and NSIP, enlarged MLNs predict survival, are associated with increased number of hospitalizations, and show signs of poorer lung function and more severe fibrosis.