Abstract Background In post-stroke AF patients with indications for both oral anticoagulants (OACs) and antiplatelet agents (AP), eg. those with carotid artery stenosis, there is debate over the best management strategy. Objectives We aimed to examine outcomes in post-stroke AF patients with extracranial artery stenosis (ECAS). Second, to explore stroke and bleeding outcomes as well as the net clinical benefit (NCB), with OACs (non-vitamin K antagonist OACs [NOACs] or warfarin) and with AP-OAC combination therapy, when compared to AP alone. Methods We performed a nationwide cohort study in post-stroke AF patients with and without ECAS (n=6390 and 28093, respectively). The risks of clinical events and NCB with different antithrombotic strategies were compared to AP alone. Results The risk of recurrent ischemic stroke was higher for patients with ECAS than those without (12.72%/yr versus 10.60/yr; adjusted hazard ratio [aHR] 1.104, p<1.001). For patients with ECAS, when compared to AP only, NOAC monotherapy was associated with lower risks for ischaemic stroke (aHR 0.551 [95%CI 0.454-0.669], the composite of ischaemic stroke/major bleeding (aHR 0.577 [95%CI 0.478-0.697]) and the composite of ischaemic stroke/ICH (aHR 0.577 [95%CI 0.478-0.697]), with nonsignificant difference for major bleeding and ICH (Figure). NOAC monotherapy was the only approach associated with a positive NCB, while all other options (warfarin, combination AP-OACs) were associated with negative NCB. Conclusions For post-stroke AF patients with ECAS, NOAC monotherapy was associated with lower risks of adverse outcomes and a positive NCB. Combination of AP with NOAC or warfarin did not offer any benefit, but more bleeding especially with AP-warfarin combination therapy.