Introduction: Neurological impairment is associated with collateral status in acute ischaemic stroke (AIS). We aimed to validate the association between admission National Institutes of Health Stroke Scale (aNIHSS) score and infarct core volume (ICV) and target infarct core/penumbra volume mismatch (TMM) on CT perfusion (CTP) in AIS patients. Methods: Patients with acute middle cerebral artery or internal carotid artery occlusion from 2011 to 2020 were included. All patients underwent pretreatment CTP at admission. ICV and TMM were analyzed with MIStar software on CTP maps. aNIHSS scores and clinical characteristics of patients were obtained from our prospectively recorded stroke database. Results: We recruited 182 patients with a median age of 69.5 years; 85 (63.7%) were male, and the median aNIHSS score was 14. Of those, 149 (81.8%) had an ICV < 70 mL, and 139 (76.3%) had TMM. Lower aNIHSS was associated with an ICV < 70 mL, with an area under the curve (AUC) of 0.74, and TMM with an AUC of 0.76. Among all 15 items of the aNIHSS, the gaze score was the only item independently associated with an ICV < 70 mL (adjusted odds ratio [OR] = 0.42, 95% confidence interval [CI]: 0.22–0.79, p = 0.008) and TMM (adjusted OR = 0.5, 95% CI: 0.28–0.9, p = 0.021). One or both aNIHSS ≤ 16 and gaze score = 0 predicted TMM with a sensitivity of 0.79 and a specificity of 0.62. Conclusion: aNIHSS may be a useful tool to predict an ICV < 70 mL and TMM on CTP in AIS patients.