Background: The impact of calcification on the carotid atherosclerotic plaque vulnerability remains controversial and unclear. This study assesses the critical mechanical conditions induced by the calcium at the lumen surface i.e. juxtaluminal calcification (JLCa), within human carotid atherosclerotic plaque. Methods: Eleven patients with evidence of JLCa were included for the analysis. The plaque geometry was reconstructed based on CT and MR images and 3D fluid-structure interaction simulation was used for mechanical analysis. Results: Presence of JLCa increased local stresses compared to when calcification was artificially covered with a 0.2mm-thickness FC (107.87kPa [76.99, 129.14] vs. 63.17 kPa [34.55, 75.13]; Median, [inter quartile range]; p<0.0001]. Stretch ratio decreased from 1.18 [1.07, 1.27] to 1.13 [1.10, 1.18] (p=0.03). Conclusion: The presence of JLCa significantly elevates local stress and stretch level. Further exploration of this plaque feature is warranted as a possible risk factor causing plaque vulnerability.