Abstract: Objectives: To (1) evaluate the impact of different monochromatic images produced by dual-layer spectral detector computed tomography on the overall quality of the images produced by acute anterior circulation ischemic stroke patients and (2) identify the optimal monochromatic energy level. Methods: The imaging data from 43 patients with acute anterior circulation ischemic stroke who underwent a cranial spectral computed tomography (CT) plain scan and a computed tomography perfusion imaging (CTP) examination at Weihai Central Hospital, China, were analyzed. Conventional mixed-energy images and 40–140 keV monochromatic images (at 10 keV intervals) were reconstructed and subjective and objective assessments of image quality were performed to identify the optimal monoenergetic images. ANOVA and the Friedman test were used to statistically analyze the image quality indicators and the Kappa test was applied to evaluate the inter-observer consistency. The intergroup differences in quantitative parameters between the optimal monochromatic images and the conventional images were compared. The CTP results were considered to be gold standard and ROC curves were used to compare the diagnostic efficacy of the monochromatic and conventional image groups. Results: The signal to noise ratio (SNR) of the infarct, contrast to noise ratio (CNR) of the gray matter/infarct, and CNR of the white matter/infarct in the monochromatic images were superior to those produced by the conventional images at 40–140 keV, 40–70 keV, and 40–50 keV, respectively, and the differences were statistically significant. The subjective scores for the monochromatic images showed that the contrast scores were significantly better than those of conventional images at 40–60 keV and the image noise scores were significantly better than those of the conventional images at 80–140 keV. At 50 keV, all objective evaluation indicators for the infarct region and the subjective scores for contrast were higher than those for conventional images. This energy level had a relatively high diagnostic efficacy for the core infarct area and ischemic penumbra with an AUC of 0.792, a sensitivity of 90.7%, and a specificity of 55.8%. Conclusions: The CNR, SNR, and subjective scores for acute anterior circulation ischemic stroke were higher in multiple sets of the monochromatic energy images than for the conventional images. Among the spectral CT monochromatic energy images, the 50 keV image produced the best balance among multiple indices and had a high diagnostic efficacy for the core infarct area and ischemic penumbra; therefore, 50 keV is the recommended optimal energy level for monochromatic imaging.