Introduction: Continuous medication use is essential for patients with atrial fi brillation using new oral anticoagulants. Older age and polymorbidity may affect compliance related to the anticoagulation therapy. Methods: An observational cohort study (STROBE) assessed patients' compliance with selected cardiovascular diagnoses and other comorbidities who received NOAC and outpatient care in specialized clinics in the Czech Republic in the questionnaire survey between April and May 2023. Results: Patients meeting the study criteria were approached by the treating physician for inclusion (4 cardiology and 1 neurology clinic). A total of 274 patients (146 women, 128 men) with a primary diagnosis of atrial fibrillation and at least one confirmed secondary diagnosis of heart attack, cerebral infarction, transient cerebral ischemic attack (TIA), obesity, arterial hypertension, or diabetes mellitus participated. Statistical analysis confi rmed that patients with a history of stroke or TIA had a higher number of regular follow-up visits (once every three months) (p = 0.002492). Furthermore, data analysis demonstrated that patients who had been on treatment for a shorter time tended to have more frequent regular follow-up visits (treatment duration up to 3 months/average check-ups 1.7 times; 3-5 months/0.9 times; 6-12 months/0.7 times). In one patient (55 years) with paroxysmal atrial fibrillation and a diagnosis of TIA, who declared irregularity of NOAC use for 3-5 months of treatment, a relapse of TIA was identifi ed. Conclusion: A high burden of additional comorbidities was identifi ed in the observed sample, along with the inadequate declaration of the regularity of NOAC medication use and the resulting risks. Appropriate patient education is essential, especially among older patients at a high risk of stroke, considering the increasing prescription rates.