Background: The triglyceride/glucose index (TyG) reflects insulin resistance and predicts the risk of acute ischemic stroke (aIS). However, it is uncertain if this index predicts the severity and outcome of aIS because studies that addressed this question are few and all were performed in Asian subjects. Moreover, there are no studies that focused on patients with hypercholesterolemia. Methods: We studied 997 Caucasian patients who were hospitalized for aIS and had hypercholesterolemia. aIS severity was assessed at admission with the National Institutes of Health Stroke Scale (NIHSS) and severe aIS was defined as NIHSS \ge21. The outcome was assessed with the functional outcome at discharge and with in-hospital mortality. An unfavorable functional outcome was defined as modified Rank in scale (mRs) at discharge between 3 and 6. Results: The TyG index did not correlate with the NIHSS at admission (r = 0.032, p = NS) and was similar in patients with severe and non-severe aIS (8.7 \pm 0.6 and 8.6 \pm 0.6, respectively; p = NS). Risk factors for severe aIS were age, female gender, atrial fibrillation (AF) and diastolic blood pressure (DBP) at admission. The TyG index also did not correlate with the mRs(r = 0.037, p = NS) and was similar in patients who had unfavorable and favorable functional outcome (8.7 \pm 0.6 and 8.6 \pm 0.5, respectively; p = NS). Risk factors for unfavorable functional outcome were age, previous ischemic stroke, body mass index and the NIHSS at admission. The TyG index was similar in patients who died during hospitalization and patients who were discharged (8.7 \pm 0.6 and 8.7 \pm 0.6, respectively; p = NS). Risk factors for in-hospital mortality were AF and DBP and NIHSS at admission. Conclusions: The TyG index does not appear to be associated with the severity or the outcome of aIS. Nevertheless, since there are few relevant data in Caucasians and the TyG index is an inexpensive and widely available biomarker, more studies in this ethnic group are required to determine the predictive role of this index in patients with aIS.