Objective: Three-dimensional contrast-enhanced fusion ultrasound (CEFUS) of atherosclerotic carotid arteries provides spatial visualization of the vessel lumen, creating a lumenography. As in 3-D computed tomography angiography (CTA), 3-D CEFUS outlines the contrast-filled lumen. Plaque and vessel contours are distinguished in 3-D CEFUS, allowing plaque volume quantification as a valid estimate of carotid plaque burden. Three-dimensional CEFUS is unproven in intermodality studies, vindicating the assessment of 3-D CEFUS applicability and comparing 3-D CEFUS and 3-D CTA lumenography as a proof-of-concept study. Methods: Using an ultrasound system with magnetic tracking, a linear array transducer and SonoVue contrast agent, 3-D CEFUS acquisitions were generated by spatial stitching of serial 2-D images. From 3-D CEFUS and 3-D CTA imaging, the atherosclerotic carotid arteries were reconstructed with lumenography in an offline software program for lumen and plaque volume quantification. Bland–Altman analysis was used for inter-image modality agreement. Results: The study included 39 carotid arteries. Mean lumen and plaque volume in 3-D CEFUS were 0.63 cm³ (standard deviation [SD]: 0.26) and 0.62 cm³ (SD: 0.26), respectively. Lumen volume differences between 3-D CEFUS and 3-D CTA were non-significant, with a mean difference of 0.01 cm³ (SD: 0.02, p = 0.26) and limits of agreement (LoA) range of ±0.11 cm³. Mean plaque volume difference was –0.12 cm³ (SD: 0.19, p = 0.006) with a LoA range of ±0.39 cm³. Conclusion: There was strong agreement in lumenography between 3-D CEFUS and 3-D CTA. The interimage modality difference in plaque volumes was substantial because of challenging vessel wall definition in 3-D CTA. Three-dimensional CEFUS is viable in quantifying carotid plaque volume burden and can potentially monitor plaque development over time.