BACKGROUND AND PURPOSE: Conventional CT often cannot distinguish hemorrhage from iodine extravasation following reperfusion therapy for acute ischemic stroke. We investigated the potential of spectral detector CT in differentiating these lesions. MATERIALS AND METHODS: Centrifuged blood with increasing hematocrit (5%-85%) was used to model hemorrhage. Pure blood, blood-iodine mixtures (75/25, 50/50, and 25/75 ratios), and iodine solutions (0-14 mg I/mL) were scanned in a phantom with attenuation ranging from 12 to 75 HU on conventional imaging. Conventional and virtual noncontrast attenuation was compared and investigated for correlation with calculation of relative virtual noncontrast attenuation. Values for all investigated categories were compared using the Mann-Whitney U test. Sensitivity and specificity of virtual noncontrast, relative virtual noncontrast, conventional CT attenuation, and iodine quantification for hemorrhage detection were determined with receiver operating characteristic analysis. RESULTS: Conventional image attenuation was not significantly different among all samples containing blood (P Ͼ .05), while virtual noncontrast attenuation showed a significant decrease with a decreasing blood component (P Ͻ .01) in all blood-iodine mixtures. Relative virtual noncontrast values were significantly different among all investigated categories (P Ͻ .01), with correct hemorrhagic component size estimation for all categories within a 95% confidence interval. Areas under the curve for hemorrhage detection were 0.97, 0.87, 0.29, and 0.16 for virtual noncontrast, relative virtual noncontrast, conventional CT attenuation, and iodine quantification, respectively. A Ն10-HU virtual noncontrast, Ն20-HU virtual noncontrast, Ն40% relative virtual noncontrast, and combined Ն10-HU virtual noncontrast and Ն40% relative virtual noncontrast attenuation threshold had a sensitivity/specificity for detecting hemorrhage of 100%/23%, 89%/ 95%, 100%/82%, and 100%/100%, respectively.