Background: Analyze the most important prognostic factors when performing periapical surgery and compare the success rates of distinct authors. Introduction: Periapical surgery is an approach to treat non-healing periapical lesions and it should be viewed as an extension of endodontic treatment and not as a separate entity. Material and Methods: A search of articles published in Cochrane, PubMed (MEDLINE) and Scopus was conducted with the key words “prognostic factors”, “prognosis”, “periapical surgery”, “endodontic surgery” and “surgical endodontic treatment”. The inclusion criteria were articles including at least 10 patients, published in English, for the last 10 years. The exclusion criteria were nonhuman studies and case reports. Results: 33 articles were selected from 321 initially found. Ten articles from 33 were excluded and finally the systematic review included 23 articles: 1 metaanalysis, 1 systematic review, 2 randomized clinical trials, 6 reviews, 12 prospective studies and 1 retrospective study. They were stratified according to their level of scientific evidence using the SORT criteria. Conclusions: Factors associated with a better outcome of periapical surgery are patients ≤45 years old, upper anterior or premolar teeth, ≤10 sized lesions, non cystic lesions, absence of preoperative signs and symptoms, lesions without periodontal involvement, teeth with an adequate root-filling length, MTA as root-end filling material, uniradicular teeth, absence of perforating lesions, apical resection < 3 mm, teeth not associated to an oroantral fistula and teeth with only one periapical surgery.