The aim of this paper was systematically to evaluate the caries-preventive effect of professional fluoride varnish treatments. A search of the literature for articles published between 1966 and August 2003 was carried out in electronic databases, reference lists of articles, and selected textbooks in accordance with the strategy of the Swedish Council on Technology Assessment in Health Care. Out of 302 identified papers, 24 randomized and controlled clinical trials comparing fluoride varnish with placebo, no active treatment or other fluoride preventive regimens of at least 2 years' study duration were included. The trials that met the inclusion criteria were assessed independently and systematically by at least two reviewers and scored from A to C according to predetermined criteria for methodology and performance. The main outcome measure was the preventive fraction expressed as a percentage. The results displayed limited evidence (evidence level 3) for the caries preventive effect of topical applications of fluoride varnishes in permanent teeth. The average prevented fraction was 30% (0-69%) when compared with untreated controls. Inconclusive evidence (evidence level 4) was found for fluoride varnish treatment in the primary dentition and in adults. This systematic review reinforces the need for future dinical research of high quality, incorporating modern concepts of dinical performance and evaluation to assess dental caries control using professional fluoride varnish.