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Antithrombotic treatment of frail patients with AF presents various challenges. The fear of bleeding often leds to a large underuse of anticoagulant agents in these patients, although more recent data indicate that oral anticoagulation (especially with the newer, direct anticoagulants) is increasingly used. While there is a need for more real world data, available evidence suggests that non-vitamin K antagonist oral anticoagulants (NOACs) are an effective alternative to warfarin in frail patients with AF for preventing thromboembolic events, with a better safety profile. Logical considerations and evidence-base data related to the reduced bleeding risk (also including major bleeding and intracranial bleeding) of NOACs make these drugs the anticoagulant agents of choice in frail patients; however, in this setting an individualised approach should be taken, taking into consideration the risk of thromboembolic and bleeding events, other comorbidities and patient-related factors, rather than a generalised “one drug fits all” approach.