BACKGROUND: Studies using medical images have shown that intraplaque hemorrhage may accelerate plaque progression and may produce a stimulus for atherosclerosis development by increasing lipid core and plaque volume and creating new destabilizing factors. Image-based 3D computational models with fluid-structure interactions (FSI) will be used to perform plaque mechanical analysis and investigate possible associations between intraplaque hemorrhage and both plaque wall stress (PWS) and flow shear stress (FSS). METHODS: In vivo MRI data of carotid plaques from 5 patients with intraplaque hemorrhage confirmed by histology were acquired. 3D multi-component FSI models were constructed for each plaque to obtain mechanical stresses. Plaque Wall Stress (PWS) and Flow Shear Stress (FSS) were extracted from all nodal points on the lumen surface of each plaque for analysis. RESULTS: The mean PWS value from all hemorrhage nodes of the 5 plaques combined was higher than that from non-hemorrhage nodes (75.6 versus 68.1 kPa, P = 0.0003). The mean PWS values from hemorrhage nodes for each of the 5 plaques were all significantly higher (5 out of 5) than those from non-hemorrhage nodes (P < 0.05). The mean FSS value from all hemorrhage nodes of the 5 plaques combined was 30.4% higher than that from all non-hemorrhage nodes (15.0 versus 11.5 dyn/cm2, P = 0.0002). However, the mean flow shear stress values from individual cases showed mixed results: only one out of five plaques showed mean FSS value from hemorrhage nodes was higher than that from non-hemorrhage nodes; three out of five plaques showed that their mean FSS values from hemorrhage nodes were lower than those from non-hemorrhage nodes; and one plaque showed that the difference had no statistical significance. CONCLUSION: The results of this study suggested that intraplaque hemorrhage nodes were associated with higher plaque wall stresses. Compared to flow shear stress, plaque wall stress has a better correlation with plaque component feature (hemorrhage) linked to plaque progression and vulnerability. With further validation, plaque stress analysis may provide additional stress indicators for image-based vulnerability assessment.