Objectives To investigate the relationship between the initiation time of anticoagulation after endovascular treatment (EVT) and the outcomes in atrial fibrillation (AF)-related acute ischemic stroke (AIS) patients. Methods In this prospective registry study, from March 2013 to June 2022, patients with anterior circulation territories AF-related AIS who underwent EVT within 24 h were included. The primary outcome was favorable [modified Rankin Scale (mRS) 0-1) at ninety days and the secondary outcome was hemorrhage events after anticoagulants. Factors affecting the outcomes were pooled into multivariate regression and ROC curve analysis. Results Of 234 eligible patients, there were 63 (26.9%) patients achieved a favorable outcome. The symptomatic intracranial hemorrhage (sICH), ICH, and systemic hemorrhage events after anticoagulants occurred in 8 (3.4%), 28 (12.0%), and 39 (16.7%) patients, severally. A longer EVT to anticoagulation time (p = 0.033) was associated with an unfavorable outcome (mRS 3-6). An earlier EVT to anticoagulation time was the independent risk factor of sICH (p = 0.043), ICH (p = 0.005), and systemic hemorrhage (p = 0.005). There was no significant difference in recurrent AIS/ transient ischemic attack (TIA) or mortality among patients who started anticoagulation at & LE; 4 days, & GE; 15 days, or 4 to 15 days. The optimum cut-off for initiating anticoagulants to predict a favorable outcome and hemorrhage events was 4.5 days and 3.5 days after EVT, respectively. Conclusions In AF-related AIS, the time of EVT to anticoagulation is an independent factor of the functional outcome and hemorrhage events after anticoagulation. The optimal initiate time of anticoagulant after EVT is 4.5 days.