Adhesion molecules may contribute to the development of interstitial lung disease (ILD) and have been proposed as prognostic biomarkers in idiopathic pulmonary fibrosis. Our objective was to determine whether the circulating adhesion molecules soluble intracellular adhesion molecule (sICAM)-1, soluble vascular cell adhesion molecule (sVCAM)-1 and P-selectin are associated with subclinical ILD in community-dwelling adults.The Multi-Ethnic Study of Atherosclerosis enrolled males and females aged 45–84 years from six communities in the United States in 2000–2002. High attenuation areas were defined as the percentage of imaged lung volume with attenuation −600–−250 HU on cardiac computed tomography (CT). Interstitial lung abnormalities were visually assessed on full-lung CT. Spirometry was performed on a subset of individuals. ILD hospitalisations and deaths were adjudicated.In fully adjusted analyses, higher levels of sICAM-1, sVCAM-1 and P-selectin were associated with greater high attenuation areas (2.94%, 95% CI 1.80–4.07%; 1.24%, 95% CI 0.14–2.35%; and 1.58%, 95% CI 0.92–2.23%, respectively), and greater rate of ILD hospitalisations (HR 1.36, 95% CI 1.03–1.80; 1.40, 95% CI 1.07–1.85; and 2.03, 95% CI 1.16–3.5, respectively). sICAM-1 was associated with greater prevalence of interstitial lung abnormalities (OR 1.39, 95% CI 1.13–1.71). sICAM-1 and P-selectin were associated with lower forced vital capacity (44 mL, 95% CI 12–76 mL and 29 mL, 95% CI 8–49 mL, respectively). sVCAM-1 and P-selectin were associated with increased risk of ILD death (HR 2.15, 95% CI 1.26–3.64 and 3.61, 95% CI 1.54–8.46, respectively).Higher levels of circulating sICAM-1, sVCAM-1 and P-selectin are independently associated with CT and spirometric measures of subclinical ILD, and increased rate of adjudicated ILD events among community-dwelling adults.