Accurate mechanical characterization of coronary atherosclerotic lesions remains essential for the in vivo detection of vulnerable plaques. Using intravascular ultrasound strain measurements and based on the mechanical response of a circular and concentric vascular model, E. I. Céspedes, C. L. de Korte and A. F. van der Steen developed an elasticity-palpography technique in 2000 to estimate the apparent stress–strain modulus palpogram of the thick subendoluminal arterial wall layer. More recently, this approach was improved by our group to consider the real anatomic shape of the vulnerable plaque. Even though these two studies highlighted original and promising approaches for improving the detection of vulnerable plaques, they did not overcome a main limitation related to the anisotropic mechanical behavior of the vascular tissue. The present study was therefore designed to extend these previous approaches by considering the orthotropic mechanical properties of the arterial wall and lesion constituents. Based on the continuum mechanics theory prescribing the strain field, an elastic anisotropy index was defined. This new anisotropic elasticity-palpography technique was successfully applied to characterize ten coronary plaque and one healthy vessel geometries of patients imaged in vivo with intravascular ultrasound. The results revealed that the anisotropy index-palpograms were estimated with a good accuracy (with a mean relative error of 26.8 ± 48.8%) compared with ground true solutions.