Objectives: Analyse the effectiveness of different materials and techniques used in guided tissue regeneration (GTR) applied in periapical surgery, comparing the success rate obtained in 4-wall defects and in through-and- through bone lesions as well as to establish prognostic factors. Material and Methods: A Cochrane, PubMed-MEDLINE and Scopus database search (October 2012 to March 2013) was conducted with the search terms "periapical surgery", "surgical endodontic treatment", "guided tissue regeneration", "bone regeneration", "bone grafts", "barrier membranes" and "periapical lesions" individually and next, using the Boolean operator "AND". The inclusion criteria were the use of GTR (bone graft and/or membrane barrier), clinical studies including at least 10 patients, 10 years aged articles published in English or French. The exclusion criteria were case reports and nonhuman studies. Results: 34 publications were selected from a total of 483. 9 of the 34 were excluded. Finally, the systematic review included 25 articles: 2 metaanalysis, 8 reviews, 13 prospective studies and 2 retrospective studies. They were stratified according to their level of scientific evidence using the SORT criteria. The 4-wall periapical and through-and-through lesions improve more their prognosis by combining bone grafts and barrier membranes than using these materials exclusively, respect to the control groups. The results show lower failure rates in 4-wall le - sions than in through-and-through lesions using GTR. Conclusions: The combined GTR technique (filling material and membranes) obtains a greater success rate both in 4-wall lesions and in through-and-through lesions, respect to the control groups. The use of regeneration materials seems to be more necessary in through-and-through lesions, > 5mm lesions, lower teeth and apicomarginal lesions as they have the worst healing prognosis. In function of the articles scientific quality, a type B recommendation is given in favour to the use of GTR in association of periapical surgery in case of 4-wall and through-and-through lesions.