Objectives We sought to evaluate the rate of bleeding in relation to age (<80 and ≥80 years), the quality of anticoagulation (expressed as time spent in international normalized ratio therapeutic range), and factors associated with bleeding events. Background Stroke prevention in patients with atrial fibrillation (AF) is an increasingly crucial public health target, particularly in patients ages ≥80 years. Methods We conducted a prospective observational study on 783 patients with AF on oral anticoagulant treatment (OAT). Results Patients spent a median 14%, 71%, and 15% of time below, within, and above the intended therapeutic range, respectively. No difference in OAT quality was found between patients age <80 and ≥80 years. During follow-up, 94 patients experienced bleeding complications (rate 3.7 × 100 patient/years), 37 major (rate 1.4 × 100 patient/years), and 57 minor (rate 2.2 × 100 patient/years). Different rates of major hemorrhage were observed between patients age <80 and ≥80 years (0.9 vs. 1.9 × 100 patient/years; p = 0.004). Bleeding risk also was greater in patients with a history of previous cerebral ischemic event (odds ratio OR: 2.5; 95% confidence interval: 1.3 to 4.8; p = 0.007). A Cox regression analysis confirmed age ≥80 years associated with bleeding risk (OR: 2.0). Conclusions These results indicate that the rate of major bleeding complications may be kept acceptably low also in very elderly AF patients on OAT, provided a careful management of anticoagulation is obtained.