PurposeTo determine the optimal window setting for virtual monoenergetic images (VMI) reconstructed from dual-layer spectral coronary computed tomography angiography (DE-CCTA) datasets.Material and methods50 patients (30 males; mean age 61.1 ± 12.4 years who underwent DE-CCTA from May 2021 to June 2022 for suspected coronary artery disease, were retrospectively included. Image quality assessment was performed on conventional images and VMI reconstructions at 70 and 40 keV. Objective image quality was assessed using contrast-to-noise ratio (CNR). Two independent observers manually identified the best window settings (B-W/L) for VMI 70 and VMI 40 visualization. B-W/L were then normalized with aortic attenuation using linear regression analysis to obtain the optimized W/L (O-W/L) settings. Additionally, subjective image quality was evaluated using a 5-point Likert scale, and vessel diameters were measured to examine any potential impact of different W/L settings.ResultsVMI 40 demonstrated higher CNR values compared to conventional and VMI 70. B-W/L settings identified were 1180/280 HU for VMI 70 and 3290/900 HU for VMI 40. Subsequent linear regression analysis yielded O-W/L settings of 1155/270 HU for VMI 70 and 3230/880 HU for VMI 40. VMI 40 O-W/L received the highest scores for each parameter compared to conventional (all p < 0.0027). Using O-W/L settings for VMI 70 and VMI 40 did not result in significant differences in vessel measurements compared to conventional images.ConclusionOptimization of VMI requires adjustments in W/L settings. Our results recommend W/L settings of 1155/270 HU for VMI 70 and 3230/880 HU for VMI 40.