BACKGROUND Topically applied fluoride gels have been widely used as a caries-preventive intervention in dental surgeries and school-based programs for over two decades. OBJECTIVE To determine the effectiveness and safety of fluoride gels in the prevention of dental caries in children and to examine factors potentially modifying their effect. METHODS Multiple electronic database searches, reference lists of articles, journal handsearch, selected authors and manufacturers. METHODS Randomized or quasi-randomized controlled trials with blind outcome assessment, comparing fluoride gel with placebo or no treatment in children up to 16 years during at least one year. The main outcome was caries increment measured by the change in decayed, missing and filled tooth surfaces (D(M)FS). METHODS Inclusion decisions, quality assessment and data extraction were duplicated in a random sample of one third of studies, and consensus achieved by discussion or a third party. Study authors were contacted for missing data. The primary outcome measure was the prevented fraction (PF), that is the caries increment in the treatment group expressed as a percentage of the control group. Random effects meta-analyses were performed where data could be pooled. Potential sources of heterogeneity were examined in random effects meta-regression analyses. RESULTS Twenty-five studies were included, involving 7747 children. For the 23 that contributed data for meta-analysis, the D(M)FS pooled prevented fraction estimate was 28% (95% CI, 19% to 37%; p<0.0001). There was clear heterogeneity, confirmed statistically (p<0.0001). The effect of fluoride gel varied according to type of control group used, with D(M)FS PF on average being 19% (95% CI, 5% to 33%; p<0.009) higher in non-placebo controlled trials. A funnel plot of the 23 studies indicated a relationship between prevented fraction and study precision. Only two trials reported on adverse events. CONCLUSIONS There is clear evidence of a caries-inhibiting effect of fluoride gel. The best estimate of the magnitude of this effect, based on the 14 placebo-controlled trials, is a 21% reduction (95% CI, 14 to 28%) in D(M)FS. This corresponds to an NNT of 2 (95% CI, 1 to 3) to avoid 1 D(M)FS in a population with a caries increment of 2.2 D(M)FS/year, or an NNT of 24 (95% CI, 18 to 36) based on an increment of 0.2 D(M)FS/year. There is little information concerning deciduous dentition, on adverse effects or on acceptability of treatment. Future trials should include assessment of potential adverse effects.