Background: Accurate prediction of subsequent infarct volume in acute ischemic stroke (AIS) patients helps determine appropriate interventions and prognosis. The objectives are to assess whether early multimodal CT imaging characteristics of wake-up stroke (WUS) patients could predict post-reperfusion infarct volume and evaluate the accuracy of baseline infarct and penumbra volumes for predicting follow-up infarct volume.Methods: This retrospective study included WUS patients, last seen well (LSW) >6 hours, with multimodal CT imaging at baseline. Baseline non-contrast CT (NCCT) and CT perfusion were analyzed using RAPID software, and CT angiography using maximum intensity projection. Post-reperfusion infarct volume was assessed at 24-hour following reperfusion on magnetic resonance diffusion-weighted imaging (DWI). Patients were stratified by treatment module for analyses.Results: Of 34 eligible patients, 9 (26.5%) received intravenous recombinant tissue plasminogen activator (r-tPA) alone and 25 (73.5%) received both endovascular thrombectomy (EVT) and r-tPA. All patients had a strong correlation between baseline NCCT alberta stroke program early CT score, clot burden score (CBS), Tan score, infarct volume, penumbra volume with 24-hour post-reperfusion infarct volume (respectively, r=0.172, P=0.015; r=0.118, P=0.047; r=0.149, P=0.024; r=0.311, P=0.001 and r=0.120; P=0.045). Among reperfusion therapies, WUS patients who received EVT had a significantly lower 24-hour post-reperfusion infarct volume and had a significant difference between baseline infarct volume and 24-hour post-reperfusion infarct volume (respectively, 82 vs. 14, P=0.032 and 47 vs. 14, P=0.04).Conclusions: Primarily obtained multimodal CT imaging characteristics may predict post-reperfusion infarct volume in WUS patients, and those who underwent EVT had a significantly lower post-reperfusion infarct volume.