Background Atrial fibrillation (AF), the most common cardiac arrhythmia, is a major risk factor for stroke. Rivaroxaban, an oral factor Xa inhibitor, is approved for the prevention of stroke in patients with non-valvular AF. In the pivotal phase III trial ROCKET AF, rivaroxaban demonstrated non-inferiority compared with warfarin for reducing the risk of stroke or systemic embolism (SE) in patients with AF (intention-to-treat analysis), without an increased risk of major bleeding. Superior efficacy vs. warfarin was achieved while patients were on study medication. Other direct oral factor Xa inhibitors have completed phase III clinical trials in this indication. Compared with warfarin, apixaban (in the ARISTOTLE trial) and edoxaban (in the ENGAGE-AF trial) were shown to be superior or non-inferior, respectively, for reduction in stroke or SE risk in patients with AF. Baseline stroke risk, as indicated by CHADS2 scores, was lower in patients in the ARISTOTLE and ENGAGE-AF trials than in ROCKET AF. Objectives This review discusses the main findings from ROCKET AF, specifically examining recent subgroup analyses investigating rivaroxaban use across various patient types at high risk for adverse outcomes, including those with prior stroke or transient ischaemic attack, reduced renal function, prior myocardial infarction, peripheral artery disease, heart failure or patients aged ≥ 75 years and those resident in East Asia. Conclusions These subgroup analyses demonstrate that the treatment effect for rivaroxaban vs. warfarin is broadly consistent across a wide range of patient groups, with respect to both efficacy and safety.