Abstract Background and purpose Early glycemic variability (GV) in diabetic patients is a poor prognosis factor following cardiovascular events. However, its influence on the course of acute ischemic stroke (AIS) with large vessel occlusion remains unclear. We investigated the relationship between high GV during acute stroke and three-month functional outcome among patients treated with combined intravenous thrombolysis and endovascular therapy for large vessel occlusion. Methods A single-center retrospective analysis of AIS patients with proximal intracranial occlusion who underwent thrombolysis and mechanical thrombectomy between January 2015 and May 2017. Early GV was assessed using standard deviation (SD) of blood glucose levels for the first 24 hours. The main outcome was functional status at three months as defined by the modified Rankin scale (mRS). Secondary outcomes were change in NIHSS score from baseline to 24 hours and occurrence of severe hemorrhagic transformation. Multivariate logistic regression analyses including GV, admission glycemia and mean glycemia were performed. Results Among the 93 patients evaluated, 26 had early high GV (≥ 20.9 mg/dl). High GV was associated with poor functional outcome (OR = 8.00; 95%CI [1.34–47.89]; P = 0.02) unlike admission glycemia and mean glycemia (OR = 2.92; 95%CI [0.51–16.60]; P = 0.23 and OR = 0.36; 95%CI [0.05-2.6]; p = 0.31, respectively). High GV was not associated with NIHSS at 24 hours or hemorrhagic transformation. Conclusion Acute high GV contributes to poorer functional outcome following AIS related to large vessel occlusion and should be considered as a new target in acute stroke management.Read less <