Background Current American College of Cardiology/American Heart Association guidelines suggest that for patients with atrial fibrillation who are at low risk for stroke (CHA2DS2VASc=1) (or women with CHA2DS2VASc=2) a variety of treatment strategies may be considered. However, in clinical practice, patterns of treatment in these “low-risk” patients are not well described. The objective of this analysis is to define thromboembolic event rates and to describe treatment patterns in patients with low-risk CHA2DS2VASc scores. Methods and Results We compared characteristics, treatment strategies, and outcomes among patients with a CHA2DS2VASc=0, CHA2DS2VASc=1, females with a CHA2DS2VASc=2, and CHA2DS2VASc ≥2 in ORBIT-AF (Outcomes Registry for Better Informed Treatment of Atrial Fibrillation) I & II. Compared with CHA2DS2VASc ≥2 patients (84.2%), those with a CHA2DS2VASc=0 (60.3%), 1 (69.9%), and females with a CHA2DS2VASc score=2 (72.4%) were significantly less often treated with oral anticoagulation ( P<0.0001). Stroke rates were low overall and ranged from 0 per 100 patient-years in those with CHA2DS2VASc=0, 0.8 (95% confidence interval [CI] [0.5-1.2]) in those with CHA2DS2VASc=1, 0.8 (95% CI [0.4-1.6]) in females with a CHA2DS2VASc score=2, and 1.7 (95% CI [1.6-1.9]) in CHA2DS2VASc ≥2. All-cause mortality (per 100 patient-years) was highest in females with a CHA2DS2VASc score=2 (1.4) (95% CI [0.8-2.3]), compared with patients with a CHA2DS2VASc=0 (0.2) (95% CI [0.1-1.0]), and CHA2DS2VASc=1 (1.0) (95% CI [0.7-1.4]), but lower than patients with a CHA2DS2VASc ≥2 (5.7) (95% CI [5.4-6.0]). Conclusion The majority of CHA2DS2VASc=0-1 patients are treated with oral anticoagulation. In addition, the absolute risks of death and stroke/transient ischemic attack were low among both male and females CHA2DS2VASc=0-1 as well as among females with a CHA2DS2VASc score=2. Clinical Trial Registration URL: https://www.clinicaltrials.gov . Unique identifier: NCT01701817.