Approximately 750,000 US adults per year experience a stroke. On average, the annual risk for future ischemic stroke (secondary stroke) after an initial ischemic stroke or transient ischemic attack is approximately 3% to 4%. Cardioembolic strokes account for 20% to 25% of all strokes, with nonvalvular atrial fibrillation (NVAF) considered one of the main sources of embolism; this explains up to half of all cardioembolic strokes. We present the risk factors for stroke in NVAF, risk stratification, a diagnosis of NVAF, and treatment and prevention of stroke in NVAF. We reviewed the literature by performing a PubMed search of articles focusing on secondary stroke prevention in NVAF. This review examines the findings of major clinical trials and society guidelines for secondary stroke prevention in NVAF and presents a cost-effectiveness analysis.