Introduction Single or double antiplatelet therapy (APT), primarily aspirin and clopidogrel is the cornerstone of treatment for acute ischemic stroke (AIS) and recurrent AIS. The use of point-of-care instrument in determining on-treatment platelet reactivity (OTPR) in AIS has yet to be explored. Objective We aimed to determine the trend of baseline and serial OTPR of AIS patients during admissions at a tertiary referral centre. Methodology Patients admitted with AIS and prescribed with either aspirin or clopidogrel or both were recruited from May 2017 to January 2019. Baseline platelet reactivity (D0) prior of any APT, OTPR at Day 1 (D1) and Day 3 (D3) of admission were assessed by Multiplate®. Aspirin and clopidogrel high OTPR (HOTPR) were expressed as MEA ASPI ≥300 AU*min and MEA ADP ≥468AU*min, respectively. Results and Discussion [Refer to Report]. Conclusion In patients with AIS prescribed with APT, the OTPR was significantly reduced at D3 from D1.