Patient's adherence to oral anticoagulant therapy is essential to prevent and treat thrombotic events. To assess the patients' adherence Morisky Medication Adherence Scale 8-items was used. The target population included 785 consecutive outpatients, of whom 384 were on Vitamin K Antagonists and 401 on Direct Oral Anticoagulants. Moreover, we evaluate which variable among age, gender, having experienced a thrombotic episode, time in the therapeutic range for patients on Vitamin K Antagonists, being naive and once versus twice daily drug assumption for patients on Direct Oral Anticoagulants, could affect adherence to therapy. Morisky Medication Adherence Scale 8-items score was 8 in both groups. The intentional non-adherence obtained the lowest score while the unintentional non-adherence is the most frequent problem in patients treated with either Vitamin K Antagonists or Direct Oral Anticoagulants. Age > 75 years, male gender, having experienced a thrombotic episode, being naive and assuming Direct Oral Anticoagulants twice a day were significantly associated with a higher risk to forget assuming the oral anticoagulant, to have more difficulty in remembering to take it or to bring it in case of travel or leaving home. A low percentage of time in therapeutic range was associated with a not regularly assumption of the anticoagulants. Patients treated with Vitamin K Antagonists or Direct Oral Anticoagulants show a good adherence and persistence to their oral anticoagulant therapy. Several factors have been identified to affect patients' adherence and deserve a careful attention by the doctors at the Anticoagulation Clinic. •Adherence to both oral anticoagulants VKAs and DOACs is good in patients followed-up in an Anticoagulation Clinic.•There was no difference in the adherence to therapy between patients treated with AVKs and those treated with DOACs.•The non-intentional non-adherence is the most frequent problem in patients treated with either VKAs or DOACs.•Aging, male gender, time in range <70% and a previous thrombotic event may affect adherence of patients on VKAs.•Aging, being naïve and twice daily drug assumption may affect adherence to therapy of patients on DOACs.