BACKGROUND Most of the detected increment in dental caries among children and adolescents is confined to occlusal surfaces of posterior permanent molars. Dental sealants and fluoride varnishes are much used preventive options for caries. Although the effectiveness of sealants and fluoride varnishes for controlling caries as compared with no intervention has been demonstrated in clinical trials and summarised in systematic reviews, the relative effectiveness of these two interventions remains unclear. This review is an update of one first published in 2006 and last updated in 2010. OBJECTIVE Primary objective • To evaluate the relative effectiveness of fissure sealants compared with fluoride varnishes, or fissure sealants together with fluoride varnishes compared with fluoride varnishes alone, for preventing dental caries in the occlusal surfaces of permanent teeth of children and adolescents. Secondary objectives • To evaluate whether effectiveness is influenced by sealant material type and length of follow-up.• To document and report on data concerning adverse events associated with sealants and fluoride varnishes. METHODS We searched the following electronic databases: the Cochrane Oral Health Group Trials Register (to 18 December 2015), the Cochrane Central Register of Controlled Trials (CENTRAL) (2015, Issue 11), MEDLINE via Ovid (1946 to 18 December 2015) and EMBASE via Ovid (1980 to 18 December 2015). We also searched the US National Institutes of Health Trials Register (http://clinicaltrials.gov) and the World Health Organization (WHO) Clinical Trials Registry Platform for ongoing trials. We placed no restrictions on language or date of publication when searching electronic databases. We screened the reference lists of identified trials and review articles for additional relevant studies. METHODS We included randomised controlled trials with at least 12 months of follow-up comparing fissure sealants, or fissure sealants together with fluoride varnishes, versus fluoride varnishes for preventing caries in the occlusal surfaces of permanent premolar or molar teeth, in participants younger than 20 years of age at the start of the study. METHODS Two review authors independently screened search results, extracted data and assessed risk of bias of included studies. We attempted to contact study authors to obtain missing or unclear information.We grouped and analysed studies on the basis of sealant material type (resin-based sealant and glass ionomer-based sealant: glass ionomer and resin-modified glass ionomer) and different follow-up periods. We calculated the odds ratio (OR) for caries or no caries on occlusal surfaces of permanent molar teeth. For trials with a split-mouth design, we used the Becker-Balagtas odds ratio. For continuous outcomes and data, we used means and standard deviations to obtain mean differences. We presented all measures with 95% confidence intervals (CIs).We assessed the quality of the evidence using GRADE (Grades of Recommendation, Assessment, Development and Evaluation) methods.We conducted meta-analysis using the fixed-effect model, as data from only two studies were combined. We had planned to conduct meta-analyses using a random-effects model when more than three trials were included in the meta-analysis. RESULTS In this review, we included eight trials with 1746 participants (four of the trials were new since the 2010 update). Seven trials (1127 participants) contributed to the analyses, and children involved were five to 10 years of age at the start of the trial. Sealant versus fluoride varnish Resin-based fissure sealants compared with fluoride varnishes Four trials evaluated this comparison (three of them contributing to the analyses). Compared with fluoride varnish, resin-based sealants prevented more caries in first permanent molars at two-year follow-up (two studies in the meta-analysis with pooled odds ratio (OR) 0.69, 95% confidence interval (CI) 0.50 to 0.94; P value = 0.02; I(2) = 0%; 358 children evaluated). We assessed the body of evidence as low quality. The caries-preventive benefit for sealants was maintained at longer follow-up in one trial at high risk of bias: 26.6% of sealant teeth and 55.8% of fluoride-varnished teeth had developed caries when 75 children were evaluated at nine years of follow-up. Glass ionomer-based sealants compared with fluoride varnishes Three trials evaluated this comparison: one trial with chemically cured glass ionomer and two with resin-modified glass ionomer. Researchers reported similar caries increment between study groups regardless of which glass ionomer material was used in a trial. Study designs were clinically diverse, and meta-analysis could not be conducted. The body of evidence was assessed as of very low quality. Sealant together with fluoride varnish versus fluoride varnish alone One split-mouth trial analysing 92 children at two-year follow-up found a significant difference in favour of resin-based fissure sealant together with fluoride varnish compared with fluoride varnish only (OR 0.30, 95% CI 0.17 to 0.55). The body of evidence was assessed as low quality. Adverse events Three trials (two with resin-based sealant material and one with resin-modified glass ionomer) reported that no adverse events resulted from use of sealants or fluoride varnishes. The other five studies did not mention adverse events. CONCLUSIONS Currently, scarce and clinically diverse data are available on the comparison of sealants and fluoride varnish applications; therefore it is not possible to draw clear conclusions about possible differences in effectiveness for preventing or controlling dental caries on occlusal surfaces of permanent molars. The conclusions of this updated review remain the same as those of the last update (in 2010). We found some low-quality evidence suggesting the superiority of resin-based fissure sealants over fluoride varnish applications for preventing occlusal caries in permanent molars, and other low-quality evidence for benefits of resin-based sealant and fluoride varnish over fluoride varnish alone. Regarding glass ionomer sealant versus fluoride varnish comparisons, we assessed the quality of the evidence as very low and could draw no conclusions.