OBJECTIVE: The objective of this study was to evaluate the safety and efficacy of dual antiplatelet pretreatment combined with low-dose rtPA therapy in patients with acute mild ischemic stroke, guided by multimodal MRI. METHODS: In this study, 383 patients with acute mild ischemic stroke (NIHSS ≤ 5) who had symptom onset within 4.5 hours of MRI screening were selected. Patients in the dual antiplatelet pretreatment plus low-dose rtPA group (164 cases) received dual antiplatelet therapy combined with low-dose (0.6 mg/kg) rtPA intravenous thrombolysis. Patients in the standard-dose group (112 cases) received conventional-dose (0.9 mg/kg) rtPA intravenous thrombolysis. Additionally, patients in the dual antiplatelet group who did not receive intravenous thrombolysis (107 cases) underwent 21 days of oral dual antiplatelet treatment. RESULTS: There was no significant difference in the baseline NIHSS scores among the three groups before treatment ( CONCLUSION: After dual antiplatelet pretreatment combined with low-dose rtPA intravenous thrombolysis for acute mild stroke under multimodal MRI guidance, the proportion of patients with good functional outcomes within 90 days was higher compared to the DAPT group and the standard-dose group, with statistical significance. There was no significant increase in the risk of cerebral hemorrhage compared to the standard-dose group and the DAPT group.