With improved life expectancy and the aging population, the global burden of atrial fibrillation (AF) continues to increase, and with AF comes an estimated fivefold increased risk of ischaemic stroke. Prophylactic anticoagulant therapy is more effective in reducing the risk of ischaemic stroke in AF patients than acetylsalicylic acid or dual-antiplatelet therapy combining ASA with clopidogrel. Non-vitamin K antagonist oral anticoagulants are the standard of care for stroke prevention in patients with non-valvular AF. The optimal anticoagulant strategy to prevent thromboembolism in AF patients who are undergoing percutaneous coronary intervention and stenting, those who have undergone successful transcatheter aortic valve replacement and those with embolic stroke of undetermined source are areas of ongoing research. This article provides an update on three randomized controlled trials of rivaroxaban, a direct, oral factor Xa inhibitor, that are complete or are ongoing, in these unmet areas of stroke prevention: oPen-label, randomized, controlled, multicentre study explorIng twO treatmeNt stratEgiEs of Rivaroxaban and a dose-adjusted oral vitamin K antagonist treatment strategy in patients with Atrial Fibrillation who undergo Percutaneous Coronary Intervention (PIONEER AF-PCI) trial; the New Approach riVaroxaban Inhibition of factor Xa in a Global trial vs Aspirin to prevenT Embolism in Embolic Stroke of Undetermined Source (NAVIGATE ESUS) trial and the Global study comparing a rivAroxaban-based antithrombotic strategy to an antipLatelet-based strategy after transcatheter aortIc vaLve rEplacement to Optimize clinical outcomes (GALILEO) trial. The data from these studies are anticipated to help address continuing challenges for a range of patients at risk of stroke.