ABSTRACT Patients with atrial fibrillation are at an increased risk for stroke, and many benefits from anticoagulation. Despite the emergence of direct oral anticoagulants, many patients continue to rely on warfarin for their anticoagulation due to logistical, pharmacokinetic, clinical, or patient preference issues. Previous work has suggested that outcomes of warfarin therapy are related to patient education/knowledge. We assessed knowledge of indications, benefits, and complications of warfarin therapy in 99 randomly selected patients enrolled in the Warfarin Anticoagulation Clinic at the Mayo Clinic in Florida who were taking warfarin for non-valvular atrial fibrillation. Patients were labeled as ‘knowledgeable’ or ‘not knowledgeable’ regarding warfarin therapy according to the results of a cross-sectional questionnaire. The majority of patients in both the knowledgeable and not knowledgeable groups displayed understanding that they were taking warfarin for atrial fibrillation (valvular vs non-valvular atrial fibrillation was not an included answer choice). However, there was a clear lack of knowledge amongst patients with atrial fibrillation in both groups about their stroke risk while on and off warfarin, and their risk of major bleeding or adverse events related to their warfarin therapy. There was only a significant difference between the two groups regarding their knowledge of what increases or decreases the risk of bleeding while on warfarin. There was no major difference between the groups with regards to demographic and medical characteristics, except that ‘not knowledgeable’ patients tended to have more peripheral vascular disease, ulcer disease, and moderate-severe renal disease compared to ‘knowledgeable’ patients.