Background <p>The ARAMIS trial demonstrated the non-inferiority of dual antiplatelet therapy (DAPT) to alteplase in patients with minor nondisabling ischemic stroke. We aimed to investigate whether the degree of neurological deficit can affect the benefit of DAPT versus alteplase.</p> Methods <p>On the basis of the as-treated analysis set, eligible patients with acute minor nondisabling stroke were divided into NIHSS 0–3 and NIHSS 4–5 groups, which was further subdivided into DAPT and alteplase groups. The primary outcome was excellent functional outcome, defined as a mRS score of 0–1 at 90 days, and the safety outcome was symptomatic intracerebral hemorrhage (sICH).</p> Results <p>A total of 719 patients were enrolled, including 585 in the NIHSS 0–3 group and 134 in the NIHSS 4-5 group. In the NIHSS score 0–3 group, the proportion of patients with mRS of 0–1 at 90 days was 95.5% (277/290) in the DAPT group and 92.2% (272/295) in the alteplase group. In the NIHSS score 4–5 group, the proportion of patients with mRS of 0 or 1 at 90 days was 82.7% (43/52) in the DAPT group and 90.2 % (74/82) in the alteplase group. A significant interaction effect was identified between the baseline NIHSS and treatment for the primary outcome (<i>P</i> = 0.048). There was no patient with sICH in the DAPT group.&#xa0;In the alteplase group, there were three and one patients with sICH in the NIHSS score 0–3 group and 4–5 group, respectively.</p> Conclusions <p>Among patients with minor nondisabling acute ischemic stroke presenting within 4.5 h of symptom onset, the benefit of DAPT versus alteplase may be affected by the degree of neurological deficit on admission. DAPT may be favored in patients with a mild neurologic deficit, while alteplase is favored in patients with a higher degree of neurologic deficit.</p> <p><b>Trial Registration</b></p> <p>ClinicalTrials.gov Identifier: NCT03661411.</p>