Most of the detected increment in dental caries among children above the age of six years and adolescents is confined to occlusal surfaces of posterior permanent molars. Dental sealants and fluoride varnishes are much used to prevent caries. As the effectiveness of both interventions in controlling caries as compared with no intervention has been demonstrated previously, this review aimed to evaluate their relative effectiveness. It updates a review published originally in 2006 and updated in 2010 and in 2016. Our primary objective was to evaluate the relative effectiveness of dental sealants (i.e. fissure sealant) compared with fluoride varnishes, or fissure sealants plus fluoride varnishes compared with fluoride varnishes alone, for preventing dental caries in the occlusal surfaces of permanent teeth of children and adolescents. Our secondary objectives were to evaluate whether effectiveness is influenced by sealant material type and length of follow-up, document and report on data concerning adverse events associated with sealants and fluoride varnishes, and report the cost effectiveness of dental sealants versus fluoride varnish in caries prevention. Cochrane Oral Health's Information Specialist searched the following databases: Cochrane Oral Health's Trials Register (to 19 March 2020), the Cochrane Central Register of Controlled Trials (CENTRAL) (the Cochrane Library, 2020, Issue 2), MEDLINE Ovid (1946 to 19 March 2020) and Embase Ovid (1980 to 19 March 2020). We searched the US National Institutes of Health Trials Registry (ClinicalTrials.gov) and the World Health Organization International Clinical Trials Registry Platform for ongoing trials. There were no restrictions on the language or date of publication. We included randomised controlled trials with at least 12 months of follow-up comparing fissure sealants, or fissure sealants plus fluoride varnishes, versus fluoride varnishes, for preventing caries in the occlusal surfaces of permanent posterior teeth (i.e. premolar or molar teeth), in participants younger than 20 years of age at the start of the study. At least two review authors independently screened search results, extracted data from included studies and assessed their risk of bias. 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 or glass ionomer-based sealant (glass ionomer and resin-modified glass ionomer sealant), and different follow-up periods. We calculated the odds ratio (OR) for risk of caries on occlusal surfaces of permanent molar teeth. For trials with a split-mouth design, we used the Becker-Balagtas OR. One cluster-randomised trial provided precise estimates in terms of risk ratio (RR), which we used. For continuous outcomes and data, we used means and standard deviations to obtain mean differences (MD). For meta-analysis, we used the random-effects model when we combined data from four or more studies. We presented all measures with 95% confidence intervals (CIs). We assessed the certainty of the evidence using GRADE criteria. We included 11 trials with 3374 participants aged five to 10 years when trials started. Three trials are new since the 2016 update. Two trials did not contribute data to our analysis. Sealant versus fluoride varnish Resin-based fissure sealants versus fluoride varnishes Seven trials evaluated this comparison (five contributing data). We are uncertain if resin-based sealants may be better than fluoride varnish, or vice versa, for preventing caries in first permanent molars at two to three years' follow-up (OR 0.67, 95% CI 0.37 to 1.19; I2 = 84%; 4 studies, 1683 children evaluated). One study measuring decayed, missing and filled permanent surfaces (DMFS) and decayed, missing and filled permanent teeth (DMFT) increment at two years suggested a small benefit for fissure sealant (DMFS MD -0.09, 95% CI -0.15 to -0.03; DMFT MD -0.08, 95% CI -0.14 to -0.02; 542 participants), though this may not be clinically significant. One small study, at high risk of bias, reported a benefit for sealant after four years in preventing caries (RR 0.42, 95% CI 0.21 to 0.84; 75 children) and at nine years (RR 0.48, 95% CI 0.29 to 0.79; 75 children). We assessed each of these results as having very low certainty. Glass ionomer-based sealants versus fluoride varnishes Three trials evaluated this comparison: one trial with chemically cured glass ionomer and two with resin-modified glass ionomer. Studies were clinically diverse, so we did not conduct a meta-analysis. In general, the studies found no benefit of one intervention over another at one, two and three years, although one study, which also included oral health education, suggested a benefit from sealants over varnish for children at high risk of caries. We assessed this evidence as very low certainty. Sealant plus fluoride varnish versus fluoride varnish alone One split-mouth trial analysing 92 children at two-year follow-up found in favour of resin-based fissure sealant plus fluoride varnish over fluoride varnish only (OR 0.30, 95% CI 0.17 to 0.55), which represented a clinically meaningful effect of a 77% reduction in caries after two years; however, we assessed this evidence as very low certainty. Adverse events Five trials (1801 participants) (four using resin-based sealant material and one using resin-modified glass ionomer) reported that no adverse events resulted from use of sealants or fluoride varnishes over one to nine years. The other studies did not mention adverse events. Applying fluoride varnish or resin-based fissure sealants to first permanent molars helps prevent occlusal caries, but it has not been possible in this review to reach reliable conclusions about which one is better to apply. The available studies do not suggest either intervention is superior, but we assessed this evidence as having very low certainty. We found very low-certainty evidence that placing resin-based sealant as well as applying fluoride varnish works better than applying fluoride varnish alone. Fourteen studies are currently ongoing and their findings may allow us to draw firmer conclusions about whether sealants and varnish work equally well or whether one is better than the other.