INTRODUCTION: The main objective of a root canal sealer is to provide a fluid tight seal. The purpose of this systematic meta-analysis was to determine the relative toxicity of commonly used root canal sealers like zinc oxide eugenol, calcium hydroxide, and resin-based sealers. MATERIALS AND METHODS: An online search was conducted in peer-reviewed journals listed in PubMed, Cochrane, EBSCO, and IndMed databases between 2000 and 2012). Statistical analysis was carried out by using analysis of variance (ANOVA) followed by post-hoc comparison by Bonferroni method. The comparison between toxicity at 24 h and between 3 and 7 days was done by using paired t-test for each sealer. RESULTS: At 24 h, the relative biotoxicity of the three sealers reported was insignificant (P- value 0.29), but the difference in toxicity was found significant (P < 0.001) after 3 days. CONCLUSION: Calcium hydroxide sealer and zinc oxide eugenol were found to be significantly biotoxic as compared to resin-based sealers after 3 days.
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