Objectives: e-ASPECTS has been shown to quantify acute ischemic infarction reliably. This study validates the impact of CT slice thickness (ST) on its performance.

Methods: A cohort of 258 patients with middle cerebral artery occlusion treated with mechanical thrombectomy was analyzed. e-ASPECTS scores and infarct volumes were calculated from baseline non-contrast CT using 1-mm ST (ground truth) and axial reconstructions with 2–10-mm ST. These were correlated with baseline stroke severity (NIHSS) and clinical outcome (mRS) using logistic regression.

Results: Significant differences in e-ASPECTS scores emerged with ST >6 mm (p ≤ 0.031) and infarct volumes with ST >4 mm (p ≤ 0.001). Lower e-ASPECTS and higher infarct volumes correlated with increasing NIHSS across all STs (p ≤ 0.001), with 1-mm ST showing the strongest correlation (rho = −0.38, 0.31). Similarly, lower e-ASPECTS and higher infarct volumes across all STs were linked to poor 90-day outcomes (p ≤ 0.05), with 1-mm ST providing the strongest predictive value (OR = 0.69, 1.27).

Conclusions: e-ASPECTS provides robust assessments with ST ≤4 mm, with 1-mm ST offering the highest accuracy in predicting stroke severity and clinical outcomes.