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Introduction: Ticagrelor is one of the most recent antiplatelet drugs used to treat ischemic heart disease. Its efficacy may equal or exceed aspirin in improving clinical outcomes in patients with acute ischemic stroke who are ineligible for rt-PA. Aim of the Work: We aimed at evaluating the safety (as a primary endpoint) and efficacy (as a secondary endpoint) of a 180 mg loading dose of ticagrelor given within 9 h from the onset of first-ever ischemic stroke. Methods: We conducted an open-label, randomized prospective controlled clinical trial between May 2019 and September 2020 on patients who presented with their first-ever ischemic stroke and were recruited from the emergency department, of Kafr el-sheik University Hospitals, Egypt. Eligible patients randomly received aspirin or ticagrelor loading and maintenance doses. Treatment began within 9 h of stroke onset. Results: Aspirin was given to 84 patients; ticagrelor was given to 85. There was no significant difference between the 2 groups regarding the hemorrhagic and nonhemorrhagic complications. Patients who received ticagrelor had a better outcome regarding NIHSS improvement at 2 days and 1 week or discharge and a favorable mRS score after 1 week or discharge and at 90-day follow-up. Conclusion: Ticagrelor was noninferior to aspirin regarding safety profile. Compared with aspirin, ticagrelor had a better clinical outcome based on NIHSS and mRS in first-ever acute ischemic stroke patients who received it within 9 h from symptom onset, leading to a shorter hospital stay. [ABSTRACT FROM AUTHOR]