BACKGROUND: The majority of the detected increment in dental caries among children and adolescents is confined to pit and fissure surfaces of first molars. OBJECTIVES: The objective of this study was to compare the effectiveness of pit and fissure sealants with fluoride varnishes in the prevention of dental decay on occlusal surfaces. SEARCH STRATEGY: The Cochrane Oral Health Group's Trials Register, CENTRAL, MEDLINE, EMBASE and 10 other databases were searched to November 2009. There were no language or publication restrictions. SELECTION CRITERIA: Random or quasi-random allocation study design; sealants versus fluoride varnish or sealants and fluoride varnish combination versus fluoride varnish alone; and subjects under 20 years of age. The primary outcome of interest was the increment in the numbers of carious occlusal surfaces of permanent premolars and molars. DATA COLLECTION AND ANALYSIS: Two review authors independently screened search results, extracted data and assessed the risk of bias of trials. Risk ratios (RR) were calculated for differences between intervention and control groups and in split-mouth studies for differences of paired tooth surfaces being carious or not. No data could be combined or meta-analyses undertaken due to the clinical and methodological diversity between study designs. MAIN RESULTS: Four studies were eligible for inclusion in the review. Results of one split-mouth study at low risk of bias and one cluster randomised study at moderate/high risk of bias revealed the effectiveness of pit and fissure sealants to be statistically significantly higher than an application of fluoride varnish every 6 months in preventing occlusal decays of first molars at 23 months (with a RR of 0.74, 95% confidence interval (CI) 0.58 to 0.95); and at 4 years and 9 years (with a RR of 0.42, 95% CI 0.21 to 0.84 and RR of 0.48, 95% CI 0.29 to 0.79, respectively). One small parallel group study at moderate/high risk of bias failed to find a difference between sealants and fluoride varnishes. Further, one split-mouth study at low risk of bias with 24 months of follow-up found significantly more caries on the fluoride varnished tooth surfaces, compared to sealed plus fluoride varnished surfaces, with a RR of 0.36 (95% CI 0.21 to 0.61). AUTHORS' CONCLUSIONS: There was some evidence on the superiority of pit and fissure sealants over fluoride varnish application in the prevention of occlusal decays. However, current scarce data limit recommendations on whether to apply pit and fissure sealants or fluoride varnishes on occlusal surfaces.