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BACKGROUND Some interstitial lung diseases are associated with lung cancer. However, it is unclear whether asymptomatic interstitial lung abnormalities convey an independent risk. OBJECTIVES To assess whether interstitial lung abnormalities are associated with an increased risk of lung cancer. METHODS We analyzed data from all participants in the National Lung Cancer Trial (NSLT) except for subjects with pre-existing interstitial lung disease or prevalent lung cancers. The primary analysis included those who underwent low-dose computed tomography; those undergoing chest radiography were included in a confirmatory analysis. Participants with evidence of reticular/reticulonodular opacities, honeycombing, fibrosis, or scarring were classified as having interstitial lung abnormalities. Lung cancer incidence and mortality in participants with and without interstitial lung abnormalities were compared using Poisson and Cox regression, respectively. RESULTS Of the 25,041 participants undergoing LDCT included in the primary analysis, 20.2% had interstitial lung abnormalities. Participants with interstitial lung abnormalities had higher incidence of lung cancer (IRR 1.61, 95% CI: 1.30-1.99). Interstitial lung abnormalities were associated with higher lung cancer incidence on adjusted analyses (IRR: 1.33, 95% CI: 1.07-1.65). Lung cancer-specific mortality was also greater in participants with interstitial lung abnormalities. Similar findings were obtained in the analysis of participants undergoing chest radiography. CONCLUSIONS Asymptomatic interstitial lung abnormalities are an independent risk factor for lung cancer which can be incorporated into risk score models.