We investigated the use of an automatic surgical stapler for ligation of the atrial appendage in sheep, and then applied this technique in patients. Fourteen adult sheep underwent ligation of the left atrial appendage using a surgical stapler with a rotating head and either absorbable or stainless steel staples. In 4 sheep, killed after two hours, no hemorrhage or intraatrial thrombus was observed acutely. Ten sheep were allowed to recover for 90 to 100 days, twice the expected absorption time of absorbable staples. There was complete obliteration of the left atrial appendage without evidence of intraatrial thrombus or staple migration. The absorbable staples were completely reabsorbed. We subsequently used this technique in 5 patients undergoing mitral valve procedures. There were no complications, and adequate obliteration of the atrial appendage was achieved.