BACKGROUND Topical fluoride therapy (TFT) in the form of varnish, gel, mouthrinse or toothpaste has been used extensively as a caries-preventive intervention for over three decades. OBJECTIVE To determine the effectiveness and safety of fluoride varnishes, gels, mouthrinses, and toothpastes in the prevention of dental caries in children and to examine factors potentially modifying their effect. METHODS We searched the Cochrane Oral Health Group's Trials Register (May 2000), CENTRAL (The Cochrane Library Issue 2, 2000), MEDLINE (1966 to January 2000), plus several other databases. We handsearched journals, reference lists of articles and contacted selected authors and manufacturers. METHODS Randomized or quasi-randomized controlled trials with blind outcome assessment, comparing fluoride varnish, gel, mouthrinse, or toothpaste with placebo or no treatment in children up to 16 years during at least 1 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. Authors were contacted for missing data. The primary measure of effect was the prevented fraction (PF) that is the difference in mean caries increments between the treatment and control groups expressed as a percentage of the mean increment in the control group. Random effects meta-analyses were performed where data could be pooled. Potential sources of heterogeneity were examined in random effects metaregression analyses. RESULTS There were 144 studies included. For the 133 that contributed data for meta-analysis (involving 65,169 children) the D(M)FS pooled prevented fraction estimate was 26% (95% CI, 24% to 29%; p < 0.0001). There was substantial heterogeneity, confirmed statistically (p < 0.0001), but the direction of effect was consistent. The effect of topical fluoride varied according to type of control group used, type of TFT used, mode/setting of TFT use, initial caries levels and intensity of TFT application, but was not influenced by exposure to water fluoridation or other fluoride sources. D(M)FS PF was on average 14% (95% CI, 5% to 23%; p = 0.002) higher in non-placebo controlled trials, 14% (95% CI, 2% to 26%; p = 0.25) higher in fluoride varnish trials compared with all others, and 10% (95% CI, -17% to -3%; p = 0.003) lower in trials of unsupervised home use compared with self applied supervised and operator-applied. There was a 0.7% increase in the PF per unit increase in baseline caries (95% CI, 0.2% to 1.2%; p = 0.004). CONCLUSIONS The benefits of topical fluorides have been firmly established on a sizeable body of evidence from randomized controlled trials. While the formal examination of sources of heterogeneity between studies has been important in the overall conclusions reached, these should be interpreted with caution. We were unable to reach definite conclusions about any adverse effects that might result from the use of topical fluorides, because data reported in the trials are scarce.