||Cardiovascular disease (CVD) is becoming the number one cause of death worldwide. Atherosclerotic plaque rupture and progression are closely related to most severe cardiovascular syndromes such as heart attack and stroke. Mechanisms governing plaque rupture and progression are not well understood. A computational procedure based on three-dimensional meshless generalized finite difference (MGFD) method and serial magnetic resonance imaging (MRI) data was introduced to quantify patient-specific carotid atherosclerotic plaque growth functions and simulate plaque progression. Participating patients were scanned three times (T1, T2, and T3, at intervals of about 18 months) to obtain plaque progression data. Vessel wall thickness (WT) changes were used as the measure for plaque progression. Since there was insufficient data with the current technology to quantify individual plaque component growth, the whole plaque was assumed to be uniform, homogeneous, isotropic, linear, and nearly incompressible. The linear elastic model was used. The 3D plaque model was discretized and solved using a meshless generalized finite difference (GFD) method. Four growth functions with different combinations of wall thickness, stress, and neighboring point terms were introduced to predict future plaque growth based on previous time point data. Starting from the T2 plaque geometry, plaque progression was simulated by solving the solid model and adjusting wall thickness using plaque growth functions iteratively until T3 is reached. Numerically simulated plaque progression agreed very well with the target T3 plaque geometry with errors ranging from 11.56%, 6.39%, 8.24%, to 4.45%, given by the four growth functions. We believe this is the first time 3D plaque progression simulation based on multi-year patient-tracking data was reported. Serial MRI-based progression simulation adds time dimension to plaque vulnerability assessment and will improve prediction accuracy for potential plaque rupture risk.