The present systematic review was performed to investigate if there is evidence justifying the prophylactic extraction of third molars, one of the most frequent procedures in oral surgery. A series of searches was carried out for randomized, clinical trials and systematic reviews in seven databases (MEDLINE, BBO, LILACS, Web of Science, EMBASE, BIREME and Cochrane Library), with no restrictions regarding year or language. A supplemental manual search of the references of retrieved articles was also performed. The search strategy resulted in 260 papers. Both the data extracted and the quality of each paper were evaluated independently by two reviewers. After selection based on the preestablished eligibility criteria, four papers qualified for the final analysis. A medium degree of quality and methodological consistency was found in three studies, and low quality was found in one study. No studies showed a high degree of consistency. The most significant flaw was an inadequate sample size. The results of the present review indicate a lack of scientific evidence to justify the indication of the prophylactic extraction of third molars.