Management of patients with a single CHA2DS2-VASc score risk factor is controversial. We attempt to identify the “truly low risk” AF patients who will not benefit from oral anticoagulation (OAC) treatment. Retrospective cohort analysis, all incident non-valvular AF (NVAF) cases between 2004 and 2015, and age 21 and older, with up to one thromboembolic risk factor besides sex (CHA2DS2-VASc score of up to 1 for men and up to 2 for women). A “low risk” score was created for these patients using a logistic regression model on the incidence of stroke within 30–2500 days following the NVAF diagnosis. We identified 15,621 patients. Average age was 53.7 ± 12.3 years, 56.6% male. Mean follow-up was 5.5 years. Significant predictors of ischemic stroke were age 65–74 and diabetes (2 points each), hypertension, vascular disease, and chronic kidney disease stage 2–3 (1 point each). Stroke incidence ranged from 0.8% for score 0 and up to 3.4% for scores ≤ 2. Odds ratio for stroke among patient group with a score ≤ 2 was 4.3 (2.9–6.6) compared with score 0. Our risk score’s area-under-the-curve (AUC) for prediction of stroke was 0.68 (0.65–0.71), compared with 0.60 (0.57–0.62) for the CHAD2S2-VASc score, within this low-risk group. Patients considered at low or intermediate risk using traditional risk stratification schemes, with ≥ 2 points using this proposed low-risk index (65–74 years old, diabetics or a combination of chronic renal failure and an additional risk factor), had an overall stroke risk that may justify anticoagulation therapy.