Background The benefits of a decreased slice thickness and/or in-plane voxel size in carotid MRI for atherosclerotic plaque component quantification accuracy and biomechanical peak cap stress analysis have not yet been investigated in detail because of practical limitations. Methods In order to provide a methodology that allows such an investigation in detail, numerical simulations of a T1-weighted, contrast-enhanced, 2D MRI sequence were employed. Both the slice thickness (2 mm, 1 mm, and 0.5 mm) and the in plane acquired voxel size (0.62x0.62 mm2 and 0.31x0.31 mm2) were varied. This virtual MRI approach was applied to 8 histology-based 3D patient carotid atherosclerotic plaque models. Results A decreased slice thickness did not result in major improvements in lumen, vessel wall, and lipid-rich necrotic core size measurements. At 0.62x0.62 mm2 in-plane, only a 0.5 mm slice thickness resulted in improved minimum fibrous cap thickness measurements (a 2–3 fold reduction in measurement error) and only marginally improved peak cap stress computations. Acquiring voxels of 0.31x0.31 mm2 in-plane, however, led to either similar or significantly larger improvements in plaque component quantification and computed peak cap stress. Conclusions This study provides evidence that for currently-used 2D carotid MRI protocols, a decreased slice thickness might not be more beneficial for plaque measurement accuracy than a decreased in-plane voxel size. The MRI simulations performed indicate that not a reduced slice thickness (i.e. more isotropic imaging), but the acquisition of anisotropic voxels with a relatively smaller in-plane voxel size could improve carotid plaque quantification and computed peak cap stress accuracy.