A 55-year-old woman with Rendu-Osler-Weber disease underwent surgical resection of a pulmonary arteriovenous fistula deriving from right middle lobe vessels. The fistula was 10 x 6 x 5 cm, to our knowledge, the largest ever reported. Although the major part of the fistula was well exposed through median sternotomy, extensive bleeding during dissection of feeding and drainage vessels precluded safe dissection. Total cardiopulmonary bypass was therefore used to divert the pulmonary blood flow. Anatomy was clearly delineated and connecting vessels were safely suture-closed from within the fistula without sacrificing the right middle lobe vein, which might have been damaged without cardiopulmonary bypass. The postoperative course was uneventful, and no complications associated with cardiopulmonary bypass occurred.