Objective Once plaques intrude into the lumen, the shear stress they are exposed to alters with hitherto unknown consequences for plaque composition. We investigated the relationship between shear stress and strain, a marker for plaque composition, in human coronary arteries. Methods and results We imaged 31 plaques in coronary arteries with angiography and intravascular ultrasound. Computational fluid dynamics was used to obtain shear stress. Palpography was applied to measure strain. Each plaque was divided into 4 regions: upstream, throat, shoulder and downstream. Average shear stress and strain were determined in each region. Shear stress in the upstream, shoulder, throat and the downstream region were 2.55±0.89 Pa, 2.07±0.98 Pa, 2.32±1.11 Pa and 0.67±0.35 Pa respectively. Shear stress in the downstream region was significantly lower. Strain in the downstream region was also significantly lower than the values in the other regions (0.23±0.08 % vs 0.48±0.15 %, 0.43±0.17 % and 0.47±0.12 %, for the upstream, shoulder and throat region respectively). Pooling all regions, dividing shear stress per plaque into tertiles and computing average strain showed a positive correlation: for low, medium and high shear stress, strain was 0.23±0.10 %, 0.40±0.15 % and 0.60±0.18 %, respectively. Conclusion Low strain co-localizes with low shear stress downstream of plaques. Higher strain can be found in all other plaque regions, with highest strain found in regions exposed to the highest shear stresses. This indicates that high shear stress might destabilize plaques, which could lead to plaque rupture.