BACKGROUND: National Health and Nutrition Examination Survey 2011-2012 data indicated that, in the United States, nearly one-fourth of children and over one-half of adolescents experienced dental caries in their permanent teeth. The purpose of this review was to summarize the available clinical evidence regarding the effect of dental sealants for the prevention and management of pit-and-fissure occlusal carious lesions in primary and permanent molars, compared with a control without sealants, with fluoride varnishes, or with other head-to head comparisons. TYPE OF STUDIES REVIEWED: The authors included parallel and split-mouth randomized controlled trials that included at least 2 years of follow-up, which they identified using MEDLINE (via PubMed), Embase, LILACS, the Cochrane Central Register of Controlled Trials, and registers of ongoing trials. Pairs of reviewers independently conducted the selection of studies, data extraction, risk of bias assessments, and quality of the evidence assessments by using the Grading of Recommendations Assessment, Development and Evaluation approach. RESULTS: Of 2,869 records screened, the authors determined that 24 articles (representing 23 studies) proved eligible. Moderate-quality evidence suggested that participants who received sealants had a reduced risk of developing carious lesions in occlusal surfaces of permanent molars compared with those who did not receive sealants (odds ratio [OR], 0.15; 95% confidence interval [CI], 0.08-0.27) after 7 or more years of follow-up. When the authors compared studies whose investigators had compared sealants with fluoride varnishes, they found that sealants reduced the incidence of carious lesions after 7 or more years of follow-up (OR, 0.19; 95% CI, 0.07-0.51); however, this finding was supported by low-quality evidence. On the basis of the evidence, the authors could not provide a hierarchy of effectiveness among the studies whose investigators had conducted head-to-head comparisons. The investigators of 2 trials provided information about adverse events, but they did not report any adverse events. CONCLUSIONS AND PRACTICAL IMPLICATIONS: Available evidence suggests that sealants are effective and safe to prevent or arrest the progression of noncavitated carious lesions compared with a control without sealants or fluoride varnishes. Further research is needed to provide information about the relative merits of the different types of sealant materials.