Women with atrial fibrillation are at a higher risk of stroke, despite treatment with warfarin. It is unclear if women treated with direct oral anticoagulants (DOACs) have better clinical outcomes, especially when considering the quality of anticoagulation control of warfarin. This study compared the effectiveness and safety outcomes of DOACs versus warfarin in men and women with stratifications for anticoagulation control. Patients newly diagnosed with atrial fibrillation and prescribed oral anticoagulants during 2010 to 2015 were identified using the Hong Kong clinical database. Propensity score matching was performed in men and women separately. Further analysis was conducted to stratify warfarin users according to their anticoagulation control. Cox regression was used to compare the risk of ischemic stroke or systemic embolism, intracranial hemorrhage (ICH), gastrointestinal bleeding, and all-cause mortality in the specific sex. There were 4,972 men and 4,834 women successfully matched in our cohort. Compared with warfarin, DOAC use was associated with a lower risk of ICH (hazard ratio HR: 0.16; 95% confidence interval CI: 0.06 to 0.40) and all-cause mortality (HR: 0.55; 95% CI: 0.39 to 0.77) in women but not in men. The treatment by sex interaction was significant for ICH only, and a significantly lower risk of ICH remained in the DOAC group when compared with warfarin users with good anticoagulation control (HR: 0.13; 95% CI: 0.02 to 1.00) among women only. The risks of ischemic stroke or systemic embolism and gastrointestinal bleeding with DOACs versus warfarin were comparable in both sexes. DOACs were associated with a lower risk of ICH and all-cause mortality in women only, where the association of lower ICH risk remained when compared with warfarin users with good anticoagulation control. Display omitted