Endodontic surgery has for aim to treat bone lesions due to dental-canal infections. The authors investigated the success rate of guided-tissue regeneration (GTR) in endodontic surgery for large periapical lesions.Both bone defects with eroded lingual/palatal and buccal cortex (two-wall defect: transosseous) and lesions with noneroded lingual/palatal cortex (four-wall defect) were assessed. All lesions had a diameter of least 10mm. A total of 73 teeth in 55 patients were included according to specific selection criteria. Full mucoperiosteal tissue flap were used. A straight fissure bur in a hand-piece was positioned apically and 2.5 to 3mm of the root-end were shaved away. Root-end cavities, 2.5 to 3mm deep, were prepared with ultrasonic tips. Root-ends were sealed using Super EBA. The choice of using or not GTR associated with deproteinized bovine bone for each patient wax made by a computer-generated randomized table. For cases allocated to the GTR group, the defect was filled with anorganic bovine-bone mineral and then covered with a resorbable collagen membrane. The outcome was assessed by clinical and radiographic evaluation at one-year follow-up.Sixty-nine teeth were evaluated at one year follow-up. Twenty-six cases were transosseous lesions. At the one-year follow-up, 56 teeth had successfully healed (81.2%), healing was uncertain for 10 teeth and three were classified as failure. The cases classified as uncertain healing were scheduled for another follow-up three years later.According to published data, GTR as a complement of periapical surgery is not necessary for four-wall defects. However, it may be an indication for transosseous lesions.