Background <p>Interstitial pneumonia describes a group of non-infectious, non-cancerous lung conditions with no known cause. Enlargement of the mediastinal lymph nodes is frequently seen in individuals with interstitial pneumonia and is believed to correlate with the extent of fibrotic changes in the lungs. The objective of this study is to assess the utility of mediastinal lymph node enlargement as a prognostic factor in patients with interstitial pneumonia. This cross-sectional study included 66 patients who had been diagnosed with either UIP or NSIP. We assessed the presence, size, and location of mediastinal lymph nodes as well as the extent of lung parenchymal involvement using a CT visual scoring system.</p> Results <p>The study included 66 patients diagnosed with chronic interstitial pneumonia. Patients without mediastinal lymph node had significantly better baseline FVC (mean: 69.2, SD: 14.8) and 6MWD (mean: 357.5 m, SD: 48.4) compared to those with mediastinal lymph node enlargement (mean: 51.5, SD: 16.6; p = 0.002) and (mean: 297.9 m, SD: 93.5; <i>p</i> = 0.048), respectively, with similar pattern observed at follow-up (<i>p</i> &lt; 0.001). The majority of patients without mediastinal lymph node enlargement have low visual score for parenchymal disease compared to patients with mediastinal lymph node enlargement (<i>P</i> value 0.029). Also, the majority of patients with mediastinal lymph node enlargement were previously hospitalized for respiratory causes (85%) compared to patients without mediastinal lymph node enlargement.</p> Conclusions <p>Our study concluded that enlarged mediastinal lymph nodes (easily obtained through chest CT) can be very useful baseline factor at time of diagnosis and strong predictor of disease course and clinical outcomes in patients with UIP and NSIP. Thus, radiologists should report mediastinal lymph node enlargement as a useful marker to assist clinicians in managing patients with these subtypes of chronic pulmonary fibrosis.</p>