Oral anticoagulant treatment (OAT) is increasingly used for preventing venous thromboembolic and cardiovascular disease. Our study was aimed to evaluate the efficacy and safety of OAT management in a real-practice situation, in particular in non-valvular atrial fibrillation (NVAF) patients. Among 1,596 consecutive unselected patients (follow-up, 3,364 patient-years) referring to the Anticoagulation Clinic, 558 (follow-up, 958 patient-years) suffered from NVAF. Total bleeding events were recorded in 39/558 NVAF patients (rate, 4.2/100 patient-years) and in 132/1,038 of all other patients (rate, 5.4/100 patient-years) (P<0.003). The rate of major bleeding and thrombotic complications was not different between NVAF patients and all the other patients. Considering NVAF patients, the rate of major bleeding was slightly higher in females than in males (P=0.06). NVAF females showed a higher rate of stroke than males (P=0.004). In NVAF patients the rate of bleeding complications was not different in relation to age; instead, total and major thrombotic events occurred more frequently in patients >or= 75 years than in younger patients (P=0.05 and P=0.01, respectively). NVAF patients on OAT show a low rate of complications. However, females show a trend to higher risk of bleeding complications and suffered more frequently from stroke with respect to males in spite of therapy.