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Background: The availability of intravenous tissue plasminogen activator (IV-tPA) remains limited worldwide, especially in low-income countries, where the burden of disability due to ischemic stroke is the highest., Aims: To evaluate outcomes and safety of IV-tPA at the only Peruvian reference institute for neurologic diseases., Methods: We conducted a prospective, observational study of stroke patients who received IV-tPA between 2009 and 2016. We assessed characteristics associated with good outcome (modified Rankine scale 0-2) at 3 months using a multivariate regression model; and factors correlated with clinical improvement (delta National Institute of Health Stroke Scale (NIHSS)) using linear regression., Results: Only 1.98% (39/1,1962) of patients presenting with ischemic stroke received IV-tPA. Nearly half (41%) were younger than 60 years, 56.4 % were men, and most strokes were cardioembolic (46.2%). The majority (64.1%) were treated within 3-4.5 hours. The median NIHSS on admission and discharge was 9 and 4, respectively; 42.1% of patients had an mRS of 0-1 at 3 months. Three patients (7.7%) developed hemorrhagic conversion, and 1 patient died (2.6%). Patients with good outcomes had lower pretreatment systolic blood pressure (138.9 versus 158.1 mm Hg, P < .007), fewer complications during hospitalization (5 versus 9 events, P < .001), shorter hospital stay (14 versus 21 days, P < .03) and, paradoxically, longer last known well -to-door times (148.3 versus 105 minutes, P < .0022). Clinical improvement was associated with shorter door-to-tPA times and obesity., Conclusions: Our findings indicate that IV-tPA has similar safety and outcomes compared to developed countries. All internal metrics (door-to-tPA, door-to-CT, and CT-to-tPA time) improved over time, highlighting areas for future implementation science studies to further expedite the administration of IV-tPA., (Copyright © 2020 Elsevier Inc. All rights reserved.)