Hyperglycemia has been claimed to be associated with hemorrhagic transformation (HT) in patients with acute ischemic stroke treated with thrombolysis. The aim of this study was to assess whether the admission blood glucose level is related to HT in a prospective study in consecutive patients with acute ischemic stroke. Consecutive patients admitted for ischemic stroke to 4 Italian hospitals were included in this prospective cohort study. Among 1,125 consecutive patients included in the analysis, 98 (8.7%) had HT: 62 (5.5%) had hemorrhagic infarction (HI) and 36 (3.2%) parenchymal hematoma (PH). A blood glucose level> 110 mg/dl was found in 42.4% of the patients, a level between 110 and 149 mg/dl in 25.2%, and a level> 150 mg/dl in 17.2%. At 3 months, 7 patients were lost at follow-up, 326 patients (29.2%) were disabled (modified Rankin score≥ 3) and 129 died (11.5%). PH was associated with an increased risk of death or disability (OR 15.29, 95% CI 2.35–99.35). However, this was not the case for HT overall and HI. At logistic regression analysis, PH was predicted by high levels of admission blood glucose (OR 1.01, 95% CI 1.00–1.01 for 1 added mg/dl). The rate of PH was 2.1% in patients with< 110 mg/dl, 3.6% in patients with a level between 110 and 149 mg/dl and 6.4% in patients with a level> 150 mg/dl. The curve estimation regression model showed a significant linear increase in the risk of PH related to an increase in blood glucose levels (R 2= 0.007, p= 0.007). Hyperglycemia during acute ischemic stroke predisposes to PH, which in turn determines a nonfavorable outcome at 3 months. This relationship seems to be linear.