The objective of this study was to investigate the in vivo effectiveness of laser in the prevention of enamel demineralization during orthodontic treatment. A search of electronic databases (PubMed, ScienceDirect, Google Scholar, Scopus, the Cochrane Central Register of Controlled Trials-CENTRAL, OpenGrey, and ProQuest Dissertations and Theses-PQDT Open from ProQuest) was carried out. In vivo studies, randomized and/or controlled clinical trials regarding the use of laser treatment to prevent enamel demineralization during orthodontic treatment were included. The risk of bias of the studies included was assessed independently by 2 authors according to Cochrane guidelines. Eight articles were identified, comprising a total of 183 patients. Significant differences were observed in enamel demineralization between laser-irradiated and control groups for all laser types: argon laser, CO 2 laser, neodymium-doped yttrium aluminum garnet (Nd:YAG) laser, and Optodan ® laser, except for argon laser application for curing bracket adhesives, where no statistically significant differences were noted. Laser irradiation may be effective in inhibiting demineralization during orthodontic treatment, but there is a need for further randomized, controlled clinical trials, utilizing different laser systems to determine real clinical efficacy of the technique.