Resin sealants have been used preventively and therapeutically in tooth enamel. The latter can present different conditions in its structure. In this sense, adhesive retention in enamel has ample evidence of its effectiveness, but not in enamel with structural alterations. In this way, it is relevant to know the adhesive retention of these materials and how they behave over time in enamel with variations in its composition. To determine the retention rate of resin sealants in tooth enamel with structural alterations. The study is part of a systematic review following the PRISMA protocol. Articles published between 2010 and 2020 on the retentive behavior of resin sealants in dental with structural alterations were examined. The electronic search was carried out in Web of Science, Scopus, PubMed and Medline. Those articles that used resin sealants in dental enamel with structural alterations were incorporated in clinical trials. Results: Eight articles were found. These were stratified according to the application surface; (i) carious surface, (ii) surface with fluorosis and (iii) surface with hypomineralization of the molar incisor. It was evidenced that the retention rate of resin sealants on decayed enamel is 80% on average, in enamel with dental fluorosis 67.5% and enamel with hypomineralization of the molar incisor 72% 2 years after their application. The retentive behavior of resin sealants on enamel with structural alterations is adequate for the three application surfaces. However, further studies are required regarding dental fluorosis and molar incisor hypomineralization. The most significant evidence on the retention rate was found on various surfaces.