Introduction: Thrombolytic therapy in acute ischemic stroke has been approved for treatment of acute stroke for past two decades. However, identification of predictors of poor outcome after the intravenous (IV) alteplase therapy in acute stroke patients is a matter of research. The present study was conducted with the aim of identifying poor prognostic factors in patients of acute ischemic stroke patients. Methods: The data of 31 acute stroke patients treated with alteplase were gathered to identify the factors that were independent predictors of the poor outcome. Outcome was dichotomized using modified Rankin scale (mRS) score and National Institutes of Health Stroke Scale (NIHSS) score at 3 months after treatment into good outcome mRS - 0-2 and poor outcome mRS - 3-6. Predictors of poor outcome were analyzed. Results: Good outcome ( mRS - score 0-2) was seen in 15 (48.4%) patients with median age of ( 60) and poor outcome ( mRS - score 3-6) was seen in 16 ( 51.6%) patients median age of 75 years, which was statistically significant with the P = 0.002. The presence of risk factors such as hypertension, diabetes, dyslipidemia, smoking, alcohol intake, history of stroke, coronary artery disease, and rheumatic heart disease among the two groups did not seem influence outcome. The severity of stroke as assessed by NIHSS score at the time of presentation was significantly higher among the patients with poor outcome, with P = 0.01. Conclusion: Advance age and higher NIHSS score at the time of onset of stroke and are the independent predictors of the poor outcome after thrombolysis with IV alteplase treatment in acute ischemic stroke patients.