Several studies have investigated the effect of bleaching on dental tissues. The evaluation of the effect of home bleaching with 10% carbamide peroxide is important for assessing alterations in enamel microhardness that may affect dental health in terms of resistance to masticatory forces. This meta-analysis was performed in order to determine scientific evidence regarding the effects of home vital bleaching with 10% carbamide peroxide gel on the microhardness of human dental enamel. A systematic electronic literature search was conducted in the PubMed and Web of Science databases using search terms. Two independent researchers evaluated the information and methodological quality of the studies. Inclusion and exclusion criteria were established for article selection; further, only studies published in English were selected. Thirteen studies that met all of the inclusion and exclusion criteria were selected and underwent statistical analysis. The results of this meta-analysis showed no significant changes in enamel microhardness when using the 10% carbamide peroxide bleaching gel over periods of 7, 14 and 21 days.