Background: In select patients with minor ischemic stroke, dual antiplatelet therapy (DAPT) with aspirin plus clopidogrel is recommended if initiated early and continued for 21 to 90 days. Dual antiplatelet therapy use, in a broader population, has shown to increase the risk of bleeding without an increased antithrombotic benefit. An ongoing area of uncertainty is whether DAPT would benefit the nonminor stroke population when continued for 21 to 90 days.?s Objective: To describe the effects of DAPT after a nonminor stroke. Methods: This single-center, retrospective cohort study included patients initiated on antiplatelet therapy started within 1 week of symptom onset for a nonminor ischemic stroke from January 2013 to January 2020. Patients with any bleeding disorder or National Institutes of Health Stroke Scale score <4 were excluded. The primary endpoint was major bleeding at 3 months. Secondary endpoints included recurrent stroke and minor bleeding. Results: A total of 158 patients met criteria for inclusion. Ninety (57%) received DAPT, and 68 (43%) received single antiplatelet therapy (SAPT). The primary endpoint occurred in 3 patients in the DAPT group and 1 patient in the SAPT group ( P = 0.463). Minor bleeding occurred in 1 patient receiving DAPT and 2 patients receiving SAPT ( P = 0.402). There were 10 patients in the DAPT group and 5 patients in the SAPT group who experienced recurrent stroke or transient ischemic attack ( P = 0.429). Limitations of this study include the retrospective single-center study design. Conclusion: There was a comparable risk of bleeding and recurrent stroke between DAPT and SAPT in patients admitted with an acute nonminor stroke.