- Objectives This study sought to identify the differences in stroke, mortality, and bleeding between men and women with atrial fibrillation (AF). Background There are inconsistent data regarding the thromboembolic risk difference between men and women with AF. The authors assessed the risk of stroke, death, and bleeding in men and women with incident AF. Methods The authors employed a prospective historical cohort using an electronic database from a large health maintenance organization. All members with incident AF between 2004 and 2015 were included. Primary endpoints were ischemic stroke, death, and major bleeding. Results The authors identified 89,213 members with incident nonvalvular atrial fibrillation (NVAF), 52.3% of whom were women. Women were older, with a higher prevalence of hypertension, whereas more men had diabetes, heart failure, and ischemic heart disease than the women did. Ischemic stroke occurred in 6.4% of the patients: 7.0% of women and 5.8% of men. Gender did not affect adjusted stroke risk (hazard ratio [HR]: 0.91; 95% confidence interval [CI]: 0.77 to 1.06; p = 0.22). However, women 75 years of age and older were at an increased risk (HR: 1.25; 95% CI: 1.17 to 1.34). Mortality rates were higher among women (33.5% vs. 32%; p < 0.001); however, women had a significantly lower adjusted mortality risk (HR: 0.78; 95% CI: 0.71 to 0.86). Women had lower risk of intracranial hemorrhage (HR: 0.81; 95% CI: 0.76 to 0.87) and major gastrointestinal bleeding (HR: 0.78; 95% CI: 0.70 to 0.87). Conclusions Men and women with AF had a similar risk of ischemic stroke, except for women 75 years of age or older, who had a higher risk. Our findings support using a similar anticoagulation strategy for prevention of stroke in men and women with a similar number of risk factors.