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Background: Use of non-vitamin K antagonist oral anticoagulants (NOACs) for stroke prevention in non-valvular atrial fibrillation (NVAF) is common and significantly reduces stroke occurrence. Yet little is known about patients who have a stroke despite treatment. Objective: The aim of this work was to study the epidemiology of patients with stroke despite being treated with NOACs. Methods: We identified a cohort of patients with NVAF admitted to the United Christian Hospital for acute ischemic stroke (AIS) or transient ischemic attack (TIA) while on NOACs. The baseline characteristics, type of NOAC, compliance, duration of use, and dosage were reviewed. Results: Of 2,090 patients admitted for AIS/TIA from 2012 to 2019, 143 were on NOACs before the index episode. After excluding patients with non-compliance and incomplete data, 109 patients were included in the analysis; 65.1% were female and 79.8% were never smokers, with a mean age of 78 years. The mean CHA2DS2-VASc score was 5; 83.5% had hypertension, 59.3% had hyperlipidemia, and 30.3% had diabetes mellitus. Overall, 52.9% presented with lacunar syndrome, suggesting an atherosclerotic cause of stroke. However, their risk factor control was unexpectedly good; none had HbA1c >7% and only 23.9% had a low-density lipoprotein cholesterol level higher than 2.6 mmol/L. Conclusions: Stroke developed in NVAF patients despite being on NOACs, with the majority being female, older, and hypertensive. Surprisingly, in general they had reasonable lipid and diabetic control.