Atherosclerotic plaque rupture is recognized as the primary cause of cardiac and cerebral ischaemic events. High structural plaque stresses have been shown to strongly correlate with plaque rupture. Plaque stresses can be computed with finite-element (FE) models. Current FE models employ homogeneous material properties for the heterogeneous atherosclerotic intima. This study aimed to evaluate the influence of intima heterogeneity on plaque stress computations. Two-dimensional FE models with homogeneous and heterogeneous intima were constructed from histological images of atherosclerotic human coronaries ( n = 12). For homogeneous models, a single stiffness value was employed for the entire intima. For heterogeneous models, the intima was subdivided into four clusters based on the histological information and different stiffness values were assigned to the clusters. To cover the reported local intima stiffness range, 100 cluster stiffness combinations were simulated. Peak cap stresses (PCSs) from the homogeneous and heterogeneous models were analysed and compared. By using a global variance-based sensitivity analysis, the influence of the cluster stiffnesses on the PCS variation in the heterogeneous intima models was determined. Per plaque, the median PCS values of the heterogeneous models ranged from 27 to 160 kPa, and the PCS range varied between 43 and 218 kPa. On average, the homogeneous model PCS values differed from the median PCS values of heterogeneous models by 14%. A positive correlation ( R 2 = 0.72) was found between the homogeneous model PCS and the PCS range of the heterogeneous models. Sensitivity analysis showed that the highest main sensitivity index per plaque ranged from 0.26 to 0.83, and the average was 0.47. Intima heterogeneity resulted in substantial changes in PCS, warranting stress analyses with heterogeneous intima properties for plaque-specific, high accuracy stress assessment. Yet, computations with homogeneous intima assumption are still valuable to perform sensitivity analyses or parametric studies for testing the effect of plaque geometry on PCS. Moreover, homogeneous intima models can help identify low PCS, stable type plaques with thick caps. Yet, for thin cap plaques, accurate stiffness measurements of the clusters in the cap and stress analysis with heterogeneous cap properties are required to characterize the plaque stability.