Currently, carotid risk assessment is based on measuring the degree of stenosis to determine if carotid endarterectomy should be offered symptomatic patients (NASCET, 1991; ECST, 1991; Rothwell et al., 2003a). However, there is growing evidence that morphological composition rather than degree of luminal stenosis may be the deciding factor in determining plaque vulnerability (Virmani et al., 2006; Gronholdt et al., 1998; Falk, 1992). In particular, large lipid cores with thin fibrous caps have been determined to be the hallmark of unstable plaques at high risk of rupture. Through the advent of high-resolution MR imaging combined with computational analysis, in-vivo estimations of mechanical stresses in the fibrous cap have been enabled (Li et al., 2007; Tang et al., 2004; Zhao et al., 2002). In a recent study by Li et al. (Li et al., 2006b), the effect of stenosis severity and fibrous cap thickness on resulting mechanical stress levels was investigated. This study showed that plaques with a degree of stenosis at 70% or above all gave rise to high fibrous cap stress levels regardless of fibrous cap width. Plaques with lower degrees of stenosis also reached high stress levels depending on the thickness of the fibrous cap. However, to simplify the computational analysis a straight tube without bifurcation was used and the plaque was modeled as a large homogeneous lipid core covered by a fibrous cap of varying thickness. In our study, we used an idealized bifurcation model based on geometry obtained from a patient awaiting carotid endarterectomy. Ellipsoidally shaped lipid cores were used to create heterogeneous plaques with varying position of the lipid cores allowing for examinations of the effects of lipid core size and position in addition to the effects of the degree of stenosis and fibrous cap width. To account for the effect of increasing degrees of stenosis on fluid flows, the internal carotid artery was modeled as a Venturi tube, and the velocities adjusted accordingly. The findings of Li et al. (Li et al., 2006b) were confirmed; increasing degrees of stenosis and decreasing fibrous cap thicknesses were found to affect peak principal stress levels severely (fig. 5). Though decreases in fibrous cap width was by far the most influential parameter on fibrous cap stress levels it cannot stand alone. Lipid core sizes also impacted mechanical stress levels significantly (fig. 5) and a comprehensive approach towards fibrous cap mechanical stress estimations is deemed important. In an angiographic study of plaque ulceration, Lovett (Lovett and Rothwell, 2003) determined ulcerations to be asymmetrically distributed longitudinally with the majority occurring upstream to the plaque rather than downstream. To investigate if this phenomenon could be attributed to mechanical stress levels, symmetrical simulations were performed with lipid cores placed proximally and distally inside the plaque. However, no significant differences were found between models with proximal cores vs. distal cores, indeed the stress levels were virtually identical except for very small lipid cores (fig. 5). This effect may be due to the modeling of the internal carotid artery as a Venturi tube keeping the pressure difference across the stenosis constant. Thus a second round of simulations was performed using the original flow values measured in the patient with a 70% degree of