Background & Objective: Acute ischemic stroke is defined as the development of sudden neurological deficits resulting from a focal injury due to vascular occlusion in the central nervous system. Intravenous tissue plasminogen activator (t-PA) therapy in these patients is an internationally accepted, evidence-based effective treatment. Previous data suggest that increased serum bilirubin may reflect the intensity of oxidative stress associated with stroke severity. This study aimed to investigate the effect of bilirubin levels on early neurological improvement after intravenous t-PA treatment and whether bilirubin is a determinant in in-hospital mortality. Methods: The determinant role of admission bilirubin levels in the severity of stroke, in-hospital mortality and early neurological improvement after intravenous t-PA was investigated. An independent association of bilirubin with mortality and neurological improvement were identified by multivariate logistic regression analysis. Results: A total of 184 ischemic stroke patients who received intravenous t-PA were included in the study. Serum direct bilirubin, indirect bilirubin, and total bilirubin of patients in the group without early improvement were significantly higher than the group with improvement (p= 0.041, p= 0.030, p= 0.026, respectively). Also, in binary logistic regression analysis, total bilirubin was found to be an independent predictor for early neurological improvement (OR 6.257, 95%CI 1.482-26.413, p=0.013). Conclusions: There was a significant relationship between the severity of the stroke and in-hospital mortality and increased serum bilirubin levels in our study. Again, there was a significant relationship between the lack of early neurological improvement after intravenous t-PA and increased serum bilirubin levels, and serum direct bilirubin levels were independent predictor of neurological improvement.