Purpose <p>Carotid artery atherosclerosis, a significant manifestation of cardiovascular disease (CVD) and leading cause of stroke, develops through a gradual process of arterial inflammation and calcification. This study explores the relationship between arterial inflammation (18&#xa0;F-FDG PET/CT) and vascular calcification (18&#xa0;F-NaF PET/CT) in the left and right common carotid arteries (LCC/RCC) and their association with CVD and thromboembolic risk in patients with subclinical atherosclerosis.</p> Methods <p>A cohort of 115 subjects (73 healthy volunteers, 42 at-risk for CVD) underwent 18&#xa0;F-NaF and 18&#xa0;F-FDG PET/CT imaging. Radiotracer uptake was quantitatively assessed by measuring the average blood-pool-corrected mean standardized uptake value (aSUVmean).</p> Results <p>Relative to healthy volunteers, at-risk subjects had greater uptake of NaF and FDG (10–22% and 16–27% higher, respectively, in both arteries, <i>p</i> &lt; 0.05). On multivariate regression, NaF aSUVmean correlated with age and BMI (<i>p</i> &lt; 0.01), and FDG aSUVmean correlated with BMI (<i>p</i> ≤ 0.01), fibrinogen (<i>p</i> &lt; 0.01 in LCC only), and total cholesterol (<i>p</i> = 0.02 in RCC only). NaF aSUVmean increased with elevated 10-year CVD risk (<i>p</i> = 0.003 in LCC only), while no significant trend was seen for FDG. NaF and FDG aSUVmean increased with elevated thromboembolic risk in both arteries (<i>p</i> &lt; 0.05). No correlations between NaF and FDG aSUVmean were observed (<i>p</i> &gt; 0.05).</p> Conclusion <p>18&#xa0;F-NaF PET/CT may serve as a prognostic tool for carotid microcalcification and subclinical atherosclerosis, while the utility of 18&#xa0;F-FDG PET/CT remains uncertain.</p> Clinical trial registration <p>“Cardiovascular Molecular Calcification Assessed by 18F-NaF PET CT (CAMONA)”, NCT01724749, <a href="https://clinicaltrials.gov/study/NCT01724749">https://clinicaltrials.gov/study/NCT01724749</a>.</p>