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Atrial fibrillation (AF) is the most common cardiac arrhythmia. This analysis aimed to determine the sex-gender differences in patients with AF enrolled in the observational AntiThrombotic Agents in Atrial Fibrillation (ATA-AF) study. The study was conducted in 360 centers in Italy. During a 4-week period, all consecutive inpatients and outpatients aged ≥18 years, with a documented primary or secondary diagnosis of AF, were included. A total of 7148 patients (47% females) were enrolled. Females were significantly older, they more frequently needed assistance and were affected by severe cognitive impairment. The preferred anti-arrhythmic strategy in both genders was heart rate control (females: 54.7%, males: 48.4%, P&lt;0.0001). Among non-valvular AF patients (n=4845, females=2139), females displayed greater prevalence of CHA₂DS₂-VASc ≥2 (96.1% <em>vs</em> 80.7%; P&lt;0.0001) and CHADS₂ ≥2 (68.2% <em>vs</em> 60.4%; P&lt;0.0001). More females were at high risk of bleeding (31.3% <em>vs</em> 26.1%; P&lt;0.0001). Oral anticoagulants (OAC) were used in 55.5% of non-valvular AF patients, less frequently in females (50.9% <em>vs</em> 59.2%; P&lt;0.0001). High hemorrhagic risk [odds ratio (OR) 5.94, 95% confidence interval (CI) 4.70-7.51], paroxysmal AF (OR 3.88, 95% CI 3.11-4.83), cognitive (OR 2.18, 95% CI 1.57-3.02) and functional impairment (OR 1.31, 95% CI 1.02-1.67) were significantly related with non-prescription of OAC, while age 75 was not (1.00, 95% CI 0.79-1.26). This study defines sex-gender differences in AF patients, including lower OAC prescription in females despite of higher thrombotic risk. Concomitant higher hemorrhagic risk and other characteristics that were more frequent in females (<em>i.e.</em>, severe cognitive and functional impairment) may at least partly explain this trend towards gender-related under-prescription of OAC.