PURPOSE: To evaluate whether dual-energy multidetector computed tomography (CT) with image postprocessing techniques enhances accuracy of calcified plaque quantification beyond the scope of single-energy multidetector CT, by using optical coherence tomography (OCT) as the reference standard. MATERIALS AND METHODS: Four atherosclerotic specimens were examined with 64-section dual-energy multidetector CT by using a novel dual-detector "double-decker" design, with stacked high- and low-energy detector arrays with 32 x 0.625-mm collimation, at 140 kVp and 400 mAs, acquiring simultaneous and isopedic low- and high-energy data sets. Additionally, combined-energy data sets were calculated, and an enhancement algorithm was proposed. Cardiac motion was simulated by an anthropomorphically moving phantom, and OCT was used as a reference standard for plaque quantification. Univariate general linear model (GLM) analysis was used to compare sizes of plaque calcifications determined with OCT with those determined with dual-energy multidetector CT, and the significance of factors such as cardiac motion was assessed. RESULTS: GLM analysis revealed that plaque quantification based on low-, high-, and combined-energy data sets differed significantly from that based on OCT (P < .001). Greater data variation occurred in smaller (<8 mm(2)) and larger (>12 mm(2)) calcifications. Comparison of calcified plaque sizes determined with OCT with those determined with the dual-energy multidetector CT enhancement algorithm revealed no significant difference (P = .550). Cardiac activity led to a slight increase in data variation in regard to OCT for corresponding static (mean, 10.2% +/- 3.2 [standard deviation]) and dynamic (13.8% +/- 4.9) dual-energy multidetector CT data sets. CONCLUSION: Dual-energy multidetector CT with novel postprocessing techniques enhanced accuracy of calcified plaque quantification by reducing effects of tissue blooming and beam hardening beyond single-energy multidetector CT.