The POINT trial evaluated the effectiveness and safety of clopidogrel plus aspirin compared to aspirin alone in patients with minor ischemic stroke or high-risk transient ischemic attack (TIA). A total of 4881 patients from 269 international sites were enrolled, with the trial halted after 84% of the anticipated participants were enrolled due to a higher risk of major hemorrhage with the combination therapy. At 90 days, major ischemic events occurred in 5.0% of patients receiving clopidogrel plus aspirin versus 6.5% in those receiving aspirin alone (hazard ratio, 0.75; 95% CI, 0.59 to 0.95; P = 0.02). Major hemorrhage occurred in 0.9% of patients in the clopidogrel plus aspirin group versus 0.4% in the aspirin group (hazard ratio, 2.32; 95% CI, 1.10 to 4.87; P = 0.02). The combination therapy reduced the risk of major ischemic events but increased the risk of major hemorrhage. The benefit of clopidogrel plus aspirin was most pronounced in the first week after the initial event, while the risk of hemorrhage remained relatively constant throughout the trial. The results suggest that while clopidogrel plus aspirin may reduce the risk of ischemic events, it also increases the risk of bleeding. The trial was funded by the National Institute of Neurological Disorders and Stroke. The findings indicate that in patients with minor ischemic stroke or high-risk TIA, clopidogrel plus aspirin is associated with a lower risk of major ischemic events but a higher risk of major hemorrhage compared to aspirin alone. The results of this trial, along with the CHANCE trial, suggest that combination antiplatelet therapy may be beneficial in certain populations, but the risk of bleeding must be carefully considered. The trial had limitations, including the exclusion of patients with moderate-to-severe stroke, cardioembolic stroke, and those who are candidates for thrombolysis or thrombectomy. The results should be interpreted with caution in these groups. The study highlights the need for careful risk-benefit assessment when considering combination antiplatelet therapy in patients with minor ischemic stroke or high-risk TIA.The POINT trial evaluated the effectiveness and safety of clopidogrel plus aspirin compared to aspirin alone in patients with minor ischemic stroke or high-risk transient ischemic attack (TIA). A total of 4881 patients from 269 international sites were enrolled, with the trial halted after 84% of the anticipated participants were enrolled due to a higher risk of major hemorrhage with the combination therapy. At 90 days, major ischemic events occurred in 5.0% of patients receiving clopidogrel plus aspirin versus 6.5% in those receiving aspirin alone (hazard ratio, 0.75; 95% CI, 0.59 to 0.95; P = 0.02). Major hemorrhage occurred in 0.9% of patients in the clopidogrel plus aspirin group versus 0.4% in the aspirin group (hazard ratio, 2.32; 95% CI, 1.10 to 4.87; P = 0.02). The combination therapy reduced the risk of major ischemic events but increased the risk of major hemorrhage. The benefit of clopidogrel plus aspirin was most pronounced in the first week after the initial event, while the risk of hemorrhage remained relatively constant throughout the trial. The results suggest that while clopidogrel plus aspirin may reduce the risk of ischemic events, it also increases the risk of bleeding. The trial was funded by the National Institute of Neurological Disorders and Stroke. The findings indicate that in patients with minor ischemic stroke or high-risk TIA, clopidogrel plus aspirin is associated with a lower risk of major ischemic events but a higher risk of major hemorrhage compared to aspirin alone. The results of this trial, along with the CHANCE trial, suggest that combination antiplatelet therapy may be beneficial in certain populations, but the risk of bleeding must be carefully considered. The trial had limitations, including the exclusion of patients with moderate-to-severe stroke, cardioembolic stroke, and those who are candidates for thrombolysis or thrombectomy. The results should be interpreted with caution in these groups. The study highlights the need for careful risk-benefit assessment when considering combination antiplatelet therapy in patients with minor ischemic stroke or high-risk TIA.