In this study, an experimental framework is described that allows pressurization of intact, human atherosclerotic carotid samples (inflation testing), in combination with ultrasound imaging. Eight fresh human carotid endarterectomy samples were successfully pressurized and tested. About 36 2-D (+t) ultrasound datasets were acquired by rotating the vessel in 10° steps (Echo-CT), from which both 3-D geometry and 3-D strain data were obtained. Both geometry and morphology were assessed with micro-CT imaging, identifying calcified and lipid rich regions. US-based and CT-based geometries were matched for comparison and were found to show good agreement, with an average similarity index of 0.71. Realistic pressure–volume relations were found for 6 out of 9 samples. 3-D strain datasets were reconstructed, revealing realistic strain patterns and magnitudes, although the data did suffer from a relatively high variability. The percentage of fat and calcifications (micro-CT) were compared with the median, 75th and 99th percentile strain values (Echo-CT). A moderate trend was observed for 75th and 99th percentile strains, higher strains were found for more lipid rich plaques, where lower strains were found for highly calcified plaques. However, an inverse numerical modeling technique is necessary for proper mechanical characterization the of plaque components, using the geometry, morphology and wall deformation as input.