<p>Early reocclusion is a significant contributor to early neurological deterioration and adverse outcomes in patients with acute ischemic stroke treated with intravenous thrombolysis (IVT) therapy. Although current guidelines recommend delaying antithrombotic therapy until 24 h after IVT to reduce hemorrhagic risks, the persistently high incidence of reocclusion has prompted the exploration of earlier antithrombotic strategies. Despite theoretical benefits, extensive research has not consistently demonstrated the efficacy of early antithrombotic interventions. Nevertheless, a recent randomized controlled trial encouragingly demonstrated that ultra-early intravenous administration of the antiplatelet agent tirofiban after IVT was effective at improving functional outcomes in non-cardioembolic stroke patients with a low risk of hemorrhage. However, the considerable heterogeneity in both antithrombotic regimens and patient populations across existing studies has obscured the identification of beneficial candidates and intervention protocols for early post-thrombolysis antithrombotic therapy. We synthesizes the current evidence regarding patient selection, drug choice, and optimal timing for early antithrombotic therapy, to explore potential improvements in post-IVT antithrombotic management, emphasizing the critical need to balance the prevention of ischemic progression with the risk of hemorrhagic transformation.</p>