Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia. Some patients are managed surgically (Cox-maze procedure) with removal of 1 or both atrial appendages. A retrospective review was performed on surgically excised atrial appendages from 86 consecutive patients with AF (2004 to 2005), at Mayo Clinic in Rochester, MN. These were compared with atrial appendages removed from 2 autopsy control groups without a history of AF (26 without heart disease, and 20 with heart disease). Compared with the 2 control groups, appendages from patients with AF contained more myocyte vacuolization, fatty infiltration, and myocardial inflammation. Among the AF patients, left atrial appendages (LAA) were larger and more likely to show fatty infiltration, endocardial fibroelastosis, and mural thrombus than were right atrial appendages (RAA); in contrast, RAA were more likely to show myocyte hypertrophy and interstitial fibrosis than were LAA. In the LAA, myocyte hypertrophy and interstitial fibrosis were more often seen in patients with long-term AF recurrence than were those who remained in normal sinus rhythm postoperatively (P=0.045 and 0.036, respectively). Given the potential clinical relevance of these findings, it is recommended that the presence or absence of hypertrophy and fibrosis, and their extent, be incorporated into the surgical pathology report of all patients undergoing resection of an atrial appendage.