We aimed to analyze the frequency of persistent hyperglycemia (PH), its implications for outcome, and to document the inpatient management of hyperglycemia. Post hoc analysis of the GLIAS (Glycemia in Acute Stroke) study, a multicenter, prospective, and observational cohort study of 476 acute ischemic stroke patients. Capillary finger-prick glucose was determined on admission and during the first 48 hours. We defined PH was defined as at least 2 values ≥155 mg/dL. Outcome (modified Rankin Scale) was evaluated at 3 months. PH developed in 117 patients (24.7%). PH was associated with poorer outcome (modified Rankin Scale score >2: 56.2% vs 28.1%; P<0.01) and higher mortality (26.7% vs 5.9%; P<0.01) than those with glycemia <155 mg/dL. PH ≥155 mg/dL was associated with a 4-fold increase in the odds of poor outcome at 3 months (odds ratio, 4.7; 95% confidence interval, 2.2-10.2) after adjustment for age, gender, hypertension, diabetes, stroke severity, admission glycemia, and infarct volume. Only 20% of patients with hyperglycemia ≥155 mg/dL received insulin on admission, with a progressive increase in the use of insulin during the following 48 hours. However, 114 (39.1%) out of 291 patients who received corrective treatment for hyperglycemia still had levels ≥155 mg/dL. PH ≥155 mg/dL is a common observation in acute ischemic stroke patients that is associated with poorer outcome and higher mortality. Almost 40% of patients maintained levels ≥155 mg/dL despite corrective treatment.