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Active smoking is associated with elevated thrombotic risk. Smoking status has recently been incorporated into the SAMe-TT2R2 (sex female, age < 60 years, medical history [more than two comorbidities], treatment [interacting drugs, eg, amiodarone for rhythm control], tobacco use [doubled], race [doubled]) score that can help predict poor international normalized ratio control in patients with atrial fibrillation (AF) treated with vitamin K antagonists (VKAs). The clinical benefit of antiplatelet therapy (APT) has been seen primarily in smokers. We hypothesized that active smoking may differently influence the risks of stroke and bleeding in patients with AF treated with VKAs or with APT. ⋯ In AF, there was a higher risk of severe bleeding in smokers, mainly in those treated with VKAs.