Author's summary We evaluated the relationship between biological sex and adverse clinical events in a contemporary atrial fibrillation (AF) cohort, mainly those taking direct oral anticoagulants, among patients with more-than-intermediate risk of stroke. Sex-based differences are noted in the outcomes of patients with AF who used anticoagulants, primarily vitamin K antagonist. The stroke or systemic embolism risk and major bleeding risk did not differ between the sexes, although women had a lower risk of all-cause mortality in contemporary anticoagulation for AF. Female may not be a risk factor for adverse clinical events associated with anticoagulation for AF.