This study evaluated the clinical significance of F-18-FDG PET/CT in patients with interstitial lung disease (ILD), by investigating the relationships between F-18-FDG PET/CT parameters and clinical indicators and by evaluating the prognostic implications of 18F-FDG PET/CT results. Methods: Ninety patients (51 men, 39 women; mean age, 55.4 y; age range, 26-78 y) with ILD who underwent F-18-FDG PET/CT were retrospectively analyzed. SUVmean was defined as the mean SUV of the less-affected lung field, SUVTF as adjusted SUVmean using tissue fraction (TF), and CTmean as the mean attenuation of the corresponding region of interest on high-resolution CT. SUVmean, SUVTF, and CTmean were compared in the 90 ILD patients and in 15 age-and sex-matched controls. Correlations of SUVmax, SUVmean, SUVTF, and CTmean with clinical indicators, including estimated percentage of forced vital capacity (%FVC), estimated percentage of diffusion capacity of the lungs for carbon monoxide (%DLco), sialylated carbohydrate antigen Krebs von den Lungen-6 (KL-6), surfactant protein D (SP-D), C-reactive protein (CRP), lactate dehydrogenase (LDH), and ILD-sex-age-physiology (GAP) index, were evaluated using the Spearman rank correlation test and the Tukey-Kramer test. A Cox proportional hazards model was used for univariate and multivariate analyses of factors associated with lung transplantation-free survival. Results: SUVmean, SUVTF, and CTmean were significantly higher in ILD patients than in healthy controls, except for CTmean in patients with a nonusual interstitial pneumonia pattern. SUVmean and CTmean were significantly correlated with %FVC, %DLco, KL-6, and SP-D; SUVTF was significantly correlated with %DLco, KL-6, SP-D, and LDH; and SUVmax was weakly correlated with KL-6 and CRP. Univariate analysis showed that SUVmean, SUVTF, sex, %FVC, %DLco, KL-6, and ILD-GAP index were significantly prognostic of lung transplantation free survival; and multivariate analysis showed that SUVmean and ILD-GAP index were independently prognostic of lung transplantation free survival. A higher SUVmean indicated a poorer prognosis, especially in patients with moderate risk based on ILD-GAP index. Conclusion: SUVmean was significantly but moderately correlated with clinical indicators, providing independent prognostic information in patients with ILD. F-18-FDG PET/CT may be helpful for monitoring and risk stratification of ILD patients.