Cyclic biomechanical stress at the lumen-intima interface plays a crucial role in the rupture of coronary plaque. We performed a comprehensive assessment of a novel angiography-based method for four-dimensional (4D) dynamic assessment of superficial wall stress (SWS) and deformation with a total of 32 analyses in virtual stenosis models with equal lumen dimensions and 16 analyses in human coronary arteries in vivo. The in silico model analyses demonstrated that the SWS, derived by the proposed global displacement method without knowledge of plaque components or blood pressure, was comparable with the result calculated by traditional finite element method. Cardiac contraction-induced vessel deformation increased SWS. Softer plaque and positive arterial remodeling, associated with a greater plaque burden, showed more variation in mean lumen diameter within the cardiac cycle and resulted in higher SWS. In vivo patient analyses confirmed the accuracy of computed superficial wall deformation. The centerlines predicted by our method at random selected time instant matched well with the actual one in angiograms by Procrustes analysis (scaling: 0.995 ± 0.018; dissimilarity: 0.007 ± 0.014). Over 50% of the maximum SWS occurred at proximal plaque shoulders. This novel 4D approach could be successfully to predict superficial wall deformation of coronary artery in vivo. The dynamic SWS might be more realistic to evaluate the risk of plaque rupture.