The purpose of this quantitative systematic review was to appraise the evidence on the caries-preventive effect of glass ionomer cement (GIC) in relation to resin-based fissure sealants. Nine English and two Portuguese databases were searched (15 January 2008). Randomized clinical trials and systematic reviews were considered for inclusion. Trial exclusion criteria were: drop-out rates > 33%; no randomization; baseline differences in groups not statistically adjusted; and no clinically important outcomes were presented. Two authors reviewed the articles independently. The outcome measure for the caries preventive effect was caries absence on sealed teeth. Of the 112 identified articles, 25 were selected for review. Of these, 14 were excluded and 11 accepted (8 trials; 3 systematic reviews). The accepted reviews provided no evidence of superiority of either sealant material. Six trials were included for meta-analysis. The pooled odds ratio was 0.96, 95% CI 0.62-1.49, indicating no difference in the caries-preventive effect of GIC and resin-based fissure sealant material. This systematic review with meta-analysis found no evidence that either material was superior to the other in the prevention of dental caries. Thus, both materials appear equally suitable for clinical application as a fissure sealant material.