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Introduction Current guidelines recommend avoiding performing IVT in DOACs-treated patients because of the possibility of transforming ischemic stroke into massive intracranial hemorrhage (ICH). Studies’ findings varied widely in literature.Aim of Study We aim to reassess the safety of IVT post- DOACs treatment.Method Four databases (PubMed, WOS, Cochrane, and Embase) were searched to identify comparative studies on patients with ischemic stroke undergoing IVT and receiving DOACs. The analyzed outcomes were symptomatic ICH (sICH), any ICH, mortality, mRS 0–2, and major bleeding. RevMan Software was used to conduct the meta-analysis.Results Eleven studies involving a total of 262250 patients were included in the meta-analysis. The findings revealed no significant difference between the 2 groups in terms of sICH (RR= 1.05, 95% CI [0.87–1.26]), any ICH (RR= 1.48, 95% CI [0.82–2.66]), or overall mortality (RR= 0.63, 95% CI [0.32–1.23]). The DOACs-treated group was more likely to achieve functional independence (mRD 0–2) at 3 months than non-DOACs group (RR= 0.41, 95% CI [0.26–0.66]). However, major bleeding was reported more in DOACs-treated group (RR= 1.53, 95% CI [1.11–2.11]).Conclusion Notably, the use of IVT in patients receiving DOACs didn’t cause life threating adverse events, such as ICH or mortality in the recent trials. Besides, they improved the mRS 0–2 in ischemic stroke patients. So, it should be reconsidered as a safe choice in the current recommendations. Further studies are required to evaluate the reversal agents, such as asidarucizumab for dabigatran and andexanet alfa for factor Xa inhibitors to reduce the observed risk of major bleeding.Conflict of Interest No