This study aimed to assess the association between increased lesion peri-coronary adipose tissue (PCAT) density and coronary 18 F-sodium fluoride ( 18 F-NaF) uptake on positron emission tomography (PET) in stable patients with high-risk coronary plaques (HRPs) shown on coronary computed tomography angiography (CTA). Coronary 18 F-NaF uptake reflects the rate of calcification of coronary atherosclerotic plaque. Increased PCAT density is associated with vascular inflammation. Currently, the relationship between increased PCAT density and 18 F-NaF uptake in stable patients with HRPs on coronary CTA has not been characterized. Patients who underwent coronary CTA were screened for HRP, which was defined by 3 concurrent plaque features: positive remodeling; low attenuation plaque (LAP) (<30 Hounsfield units [HU]) and spotty calcification; and obstructive coronary stenosis ≥50% (plaque volume >100 mm 3 ). Patients with HRPs were recruited to undergo 18 F-NaF PET/CT. In lesions with stenosis ≥25%, quantitative plaque analysis, mean PCAT density, maximal coronary motion−corrected 18 F-NaF standard uptake values (SUVmax), and target-to-background ratios (TBR) were measured. Forty-one patients (age 65 ± 6 years; 68% men) were recruited. Fifty-one lesions in 23 patients (56%) showed increased coronary 18 F-NaF activity. Lesions with 18 F-NaF uptake had higher surrounding PCAT density than those without 18 F-NaF uptake (−73 HU; interquartile range −79 to −68 HU vs. −86 HU; interquartile range −94 to −80 HU; p < 0.001). 18 F-NaF TBR and SUVmax were correlated with PCAT density (r = 0.63 and r = 0.68, respectively; all p < 0.001). On adjusted multiple regression analysis, increased lesion PCAT density and LAP volume were associated with 18 F-NaF TBR (β = 0.25; 95% confidence interval: 0.17 to 0.34; p < 0.001 for PCAT, and β = 0.07; 95% confidence interval: 0.03 to 0.11; p = 0.002 for LAP). In patients with HRP features on coronary CTA, increased density of PCAT was associated with focal 18 F-NaF PET uptake. Simultaneous assessm...