Atrial fibrillation (AF) is one of the most frequently encountered arrhythmias in the hospital. A multidisciplinary approach is required to recognize and treat AF appropriately; to limit the catastrophic consequences such as stroke, heart failure, and dementia; and to decrease the burden on the healthcare system. Hospitalization related to AF is the single largest contributor to overall cost of care in managing AF patients. In this study, we examined the trends of AF hospitalizations in the United States and assessed the effects of patient demographics and comorbid diagnoses on in-hospital mortality, length of stay, and total cost of care. Understanding these factors helps us understand the health economics of AF better. There has been a significant increase in AF hospitalizations over the last decade, with a large contribution from patients >65 years of age, especially among those >80 years of age. The overall length of hospital stay has remained unchanged; however, the cost of inpatient care has increased tremendously, from approximately $2.15 billion in 2001 to $3.46 billion in 2010. To the best of our knowledge, this is the first study to assess the trends of AF-related inpatient care at a national level from the actual hospital discharge database. Such data, although they have inherent limitations, tend to provide more accurate financial trajectory of the problem.