SMARTool aims to the development of Decision Support Systems (DSS) for the risk stratification, diagnosis, prediction and treatment of coronary artery disease (CAD). In this work, we present the results of the prediction DSS, which utilizes clinical data, imaging morphological characteristics and computational modeling results. More specifically, 263 patients were recruited in the SMARTool clinical trial and 196 patients were selected for the DSS development. Traditional risk factors, blood examinations and computed coronary tomography angiography (CCTA) were performed at two different time points with an interscan period 6.22 ± 1.42 years. Computational modeling of blood flow and LDL transport was performed at the baseline. Predictive models are built for the prediction of CAD at the follow-up. The results show that CAD can be predicted with 83% accuracy, when low ESS, high accumulation of LDL and imaging data are included in the model.