Plaque progression prediction is of fundamental significance to cardiovascular research and disease diagnosis, prevention, and treatment. Magnetic resonance image (MRI) data of carotid atherosclerotic plaques were acquired from 20 patients with consent obtained. 3D thin-layer models were constructed to calculate plaque stress and strain. Data for ten morphological and biomechanical risk factors were extracted for analysis. Wall thickness increase (WTI), plaque burden increase (PBI) and plaque area increase (PAI) were chosen as three measures for plaque progression. Generalized linear mixed models (GLMM) with 5-fold cross-validation strategy were used to calculate prediction accuracy and identify optimal predictor. The optimal predictor for PBI was the combination of lumen area (LA), plaque area (PA), lipid percent (LP), wall thickness (WT), maximum plaque wall stress (MPWS) and maximum plaque wall strain (MPWSn) with prediction accuracy = 1.4146 (area under the receiver operating characteristic curve (AUC) value is 0.7158), while PA, plaque burden (PB), WT, LP, minimum cap thickness, MPWS and MPWSn was the best for WTI (accuracy = 1.3140, AUC = 0.6552), and a combination of PA, PB, WT, MPWS, MPWSn and average plaque wall strain (APWSn) was the best for PAI with prediction accuracy = 1.3025 (AUC = 0.6657). The combinational predictors improved prediction accuracy by 9.95%, 4.01% and 1.96% over the best single predictors for PAI, PBI and WTI (AUC values improved by 9.78%, 9.45%, and 2.14%), respectively. This suggests that combining both morphological and biomechanical risk factors could lead to better patient screening strategies. Copyright © 2019 Elsevier B.V. All rights reserved.