Background Stroke represents the second leading cause of death in the world after myocardial infarction. Intravenous (IV) thrombolysis with recombinant tissue plasminogen activator (alteplase, rt-PA) is the only pharmacological therapy that was approved for treatment within 4.5 h of acute ischemic stroke (AIS) onset. We aimed to predict the 3-month outcome of AIS patients who received alteplase regarding mortality, spontaneous intra-cerebral hemorrhage (sICH), and functional outcome in comparison with non-thrombolyzed patients and to evaluate the predictors of the outcome after 3 months. Methods All the clinical, National Institute of Health Stroke Scale (NIHSS) scores, radiological, and laboratory data of 40 AIS patients and received rt-PA during the period from 2016 to 2018 were collected and analyzed retrospectively. For comparison, 40 patients, as a control group, were selected to match the alteplase group as regards the baseline data and received regular treatment, rather than rt-PA within the first 24 h, that were obtained. The outcome of the thrombolyzed patients after 3 months was evaluated in comparison with controls by using a modified ranking scale. Results After a 90-day follow-up period, the death rate was slightly higher among the rt-PA group (7.5%) in comparison with the control group (5%). sICH occurred in 7.5% of the patients in the alteplase group and in 5% of the non-thrombolyzed patients; however, this difference was not significant. More patients had a favorable outcome (mRS = 0–2) in the rt-PA group than in the control group (65% vs 60%, OR 1.38, 95% CI 0.50–3.6, P = 0.51). NIHSS score on admission, body mass index (BMI) (≥ 30), and previous transient ischemic attacks (TIA)/previous ischemic stroke were significant predictors of outcome after IV thrombolysis. Age, sex, hypertension (HTN), diabetes mellitus (DM), dyslipidemia, smoking, atrial fibrillation (AF), stroke subtype, size of infarction, and hyperdense middle cerebral artery had a non-significant effect. Conclusion After 3 months of follow-up, rt-PA had a non-significant more increase of favorable outcome with increased risk of sICH and death than controls. Baseline NIHSS, BMI, and history of TIA or previous ischemic stroke were significant predictors of outcome after thrombolysis.