•In a cohort of elderly hospitalized patients suffering from Non-valvular Atrial Fibrillation on therapy with DOACs, women and men differed in the CHA2DS2VASc score: 5.3 ± 1.3 vs 4.2 ± 1.4 points (p < 0.0001) and in the HAS-BLED score: 2.5 ± 0.7 vs 2.3 ± 0.8 points (p = 0.009), which was significantly higher in women.•In this population Cognitive Impairment (CoI) and functional disabilities are widely represented.•Female sex increases the risk of being affected by CoI by approximately 3-fold, while improving functional limitations reduces this risk by approximately 15 %.•Furthermore, CoI and depressive symptoms increase the risk of functional impairment by approximately 2-fold and 28 %, respectively, while antihypertensive and antidiabetic therapy reduce this risk by 54 % and 43 %, respectively. Atrial fibrillation (AF) represents the most common supraventricular arrhythmia, with a prevalence of 1–3 % in the world population. Growing evidences show that AF plays an important role as a risk factor for the development of cognitive impairment (CoI) and dementia, depression and functional limitation. The purpose of the study is to evaluate, in a large cohort of elderly hospitalized patients with nonvalvular AF (NVAF) on direct oral anticoagulants (DOACs) therapy, the prevalence of CoI, depression, and functional limitation, and to assess the different variables that may be detrimental or protective on the risk of CoI or functional limitation. 1004 elderly patients were enrolled, 384 men and 620 women, with a mean age of 84±7.1 years. The two groups were comparable for the main study variables, except for age, prevalence of hypertension and CKD, which were higher in women, while ischemic heart disease was higher in men. In addition, the two groups differed in the CHA2DS2VASc score 5.3 ± 1.3 vs 4.2 ± 1.4 pts (p < 0.0001) and HAS-BLED score 2.5 ± 0.7 vs 2.3 ± 0.8 pts (p = 0.009) that were significantly higher in women. Our study revealed that in a cohort of elderly patients hospitalized with AF taking DOACs, CoI and disability are widely represented, and female sex increases the risk of being affected by CoI by about 3-fold, while improvement of functional limitations reduce this risk by about 15 %. In addition, CoI and depressive symptoms increase the risk of functional impairment about 2-fold and 28 % respectively, while antihypertensive and anti-diabetic therapy reduce this risk.