Objectives: To evaluate safety, clinical feasibility, and outcome of thrombolysis treatment with recombinant tissue plasminogen activator (rt-PA) followed by hemodilution in patients with ischemic stroke. Patients and Methods: 71 patients presenting with ischemic stroke within 3 hours of onset of symptoms were given intravenous rt-PA (0,9 mg / kg total dose) followed by hemodilution treatment that started one hour after thrombolysis and was achieved by infusion of dextran 40. Those patients were compared to 71 patients treated with hemodilution only. Main outcome measures were neurologic recovery and mortality at a 3-month follow-up. Also, the incidence of symptomatic intracerebral hemorrhage (ICH) was analyzed. Results: Patients treated with rt-PA had a favorable outcome than the control group (64,79% vs. 22,54%; p = 0,0001). Also, the greater proportion of patients left with minimal or no deficit 90 days after rt-PA treatment, as compared with the control group. Treatment with rt-PA significantly reduce mortality in 90 days (1,41% vs.18,31%; p = 0,002). In the rt-PA treated group symptomatic intracranial hemorrhage occurred in 1 patient who recovered to a level of functional independence and asymptomatic intracranial hemorrhage was observed in 2 patients. Conclusion: Our results revealed improvement of neurological deficit in acute ischemic stroke patients treated with rt-PA followed by hemodilution. This pilot study shows that it may be associated with better outcomes but further studies and clinical randomized trials are needed to establish indications and administration protocols.