AbstractBackground and purposeIn ischemic stroke, the impact of short‐ versus long‐term blood glucose level (BGL) on early lesion pathophysiology and functional outcome has not been assessed. The purpose of this study was to directly compare the effect of long‐term blood glucose (glycated hemoglobin [HbA1c]) versus serum BGL on early edema formation and functional outcome.MethodsAnterior circulation ischemic stroke patients who underwent mechanical thrombectomy after multimodal computed tomography (CT) on admission were analyzed. Endpoints were early ischemic cerebral edema, measured by quantitative net water uptake (NWU) on initial CT and functional independence at Day 90.ResultsA total of 345 patients were included. Patients with functional independence had significantly lower baseline NWU (3.1% vs. 8.3%; p < 0.001) and lower BGL (113 vs. 123 mg/dL; p < 0.001) than those without functional independence, while HbA1c levels did not differ significantly (5.7% vs. 5.8%; p = 0.15). A significant association was found for NWU and BGL (ß = 0.02, 95% confidence interval [CI] 0.006–0.03; p = 0.002), but not for HbA1c and NWU (ß = −0.16, 95% CI −0.53–0.21; p = 0.39). Mediation analysis showed that 67% of the effect of BGL on functional outcome was mediated by early edema formation.ConclusionAggravated early edema and worse functional outcome was associated with elevated short‐term serum BGL, but not with HbA1c levels. Hence, the link between short‐term BGL and early edema development might be used as a target for adjuvant therapy in patients with ischemic stroke.