To investigate the feasibility of quantifying the chemical composition of coronary artery plaque in terms of water, lipid, protein, and calcium contents using dual-energy computed tomography (CT) in a simulation study. A CT simulation package was developed based on physical parameters of a clinical CT scanner. A digital thorax phantom was designed to simulate coronary arterial plaques in the range of 2–5 mm in diameter. Both non-calcified and calcified plaques were studied. The non-calcified plaques were simulated as a mixture of water, lipid, and protein, while the calcified plaques also contained calcium. The water, lipid, protein, and calcium compositions of the plaques were selected to be within the expected clinical range. A total of 95 plaques for each lesion size were simulated using the CT simulation package at 80 and 135 kVp. Half-value layer measurements were made to make sure the simulated dose was within the range of clinical dual energy scanning protocols. Dual-energy material decomposition using a previously developed technique was performed to determine the volumetric fraction of water, lipid, protein, and calcium contents in each plaque. For non-calcified plaque, the total volume conservation provides the third constrain for three-material decomposition with dual energy CT. For calcified plaque, a fourth criterion was introduced from a previous report suggesting a linear correlation between water and protein contents in soft tissue. For non-calcified plaque, the root mean-squared error (RMSE) of the image-based decomposition was estimated to be 0.7%, 1.5%, and 0.3% for water, lipid, and protein contents, respectively. As for the calcified plaques, the RMSE of the 5 mm plaques were estimated to be 5.6%, 5.7%, 0.2%, and 3.1%, for water, lipid, calcium, and protein contents, respectively. The RMSE increases as the plaque size reduces. The simulation results indicate that chemical composition of coronary arterial plaques can be quantified using dual-energy CT. By accurately quantifying the content of a coronary plaque lesion, our decomposition method may provide valuable insight for the assessment and stratification of coronary artery disease.