We assessed the prevalence of interstitial lung disease (ILD) in a cohort of smokers included in a lung cancer screening trial. Two observers independently reviewed, for the presence of findings consistent with ILD, the computed tomography (CT) examinations of 692 heavy smokers recruited by the Multicentric Italian Lung Detection (MILD) trial. Four CT patterns were considered: usual interstitial pneumonia (UIP), other chronic interstitial pneumonia (OCIP), respiratory bronchiolitis (RB) and indeterminate. Subsequently, the evolution of ILD in those subjects who had undergone a repeat CT examination after 3 yrs was assessed. The UIP pattern and the OCIP pattern were identified in two (0.3%) out of 692 and 26 (3.8%) out of 692 patients, respectively; 109 (15.7%) out of 692 patients showed CT abnormalities consistent with RB, while an indeterminate CT pattern was reported in 21 out of 692 (3%) patients. Age, male sex and current smoking status were factors associated with the presence of OCIP and UIP (combined) pattern, although the relationship did not attain statistical significance. A progression of the disease was observed in three (25%) out of 12 subjects with OCIP who underwent repeat CT after 3 yrs. Thin-section CT features of ILD, probably representing smoking-related ILD, are not uncommon in a lung cancer screening population and should not be overlooked.