Objective: The aim of our study was to determine if chronic hyperglycemia, demonstrated by elevated hemoglobin A1C (HbA1C), had an effect on outcome after IV tPA infusion for acute ischemic stroke. Materials: A comprehensive record review of diabetic patients who received IV tPA with ischemic stroke who presented to a community comprehensive stroke center during a 3-year period (2010-2013) was done. Two groups were made: HbA1C >6% and Results: A total of 1,565 patients with ischemic stroke were evaluated. Of those, 166 patients met study criteria. There were 100 patients with HbA1C over 6% (mean age 73.4, 55% female). Group A had a mean INIHSS/DNIHSS of 24.5/7.8, 13.3/10.6 and 8.65/8.23 at 180 mins, respectively. The mean change in INIHSS to DNIHSS between the 180 group with Group A was Patients with Group B had mean INIHSS/DNIHSS of 16.5/6.5, 13.23/7.6 and 11.6/6.5. The mean differences between INIHSS and DNIHSS in Group A patients in the 180 min time was 13.2 (95% CI 3.8-22.5, p=.01). The NNH for giving IV tPA to patients with HbA1C >6% versus 6% treated with IVtPA, one is harmed. This doubled when IVtPA is given after 180 mins. Conclusion: Compared with patients with HbA1C 6% have a significantly greater chance of suffering a bad outcome and incurring harm. More data needs to be collected with a larger prospective study to draw better conclusions.