The aim of this systematic review was to evaluate the frequency of micronuclei or other DNA damage in the oral mucosa of adults that have smokeless tobacco habits compared to adults that not have these habits. We searched PubMed, Scopus, Web of Science, LILACS, BBO and Cochrane Library and SIGLE. We also surveyed gray literature. We included only clinical trials that compare the frequency of micronuclei or other DNA damage in the oral mucosa of adults that have smokeless tobacco habits compared to adults that not have these habits. Quality assessments of the selected trials were evaluated by two independent reviewers, using the Effective Public Health Practice Project ? (EPHPP) with modifications. After the database screening and removal of duplicates, 2574 studies were identified. After title screening, 172 studies remained, and this number was reduced to 25 after careful examination of the abstracts. The standardized mean difference of the frequency of micronuclei between groups was 1.88, with a 95% confidence interval of 1.40 to 2.36 (p< 0.00001). In all analyses heterogeneity was detected. Despite the heterogeneity of studies, the frequency of micronuclei was significant bigger in adults who have the smokeless tobacco habit when compared to those not have this habit. The same occurred with the frequency of binucleated cells, karyolisis and karyorrhexis.