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This study evaluated the cytotoxicity of the root canal sealing materials Resilon and Epiphany versus gutta-percha, Grossman's sealer, Thermaseal, and Sealapex. Using human gingival fibroblasts the fibroblasts cultures were incubated for either 1 or 24 h to test the cytotoxicity after freshly mixing or after 24 h of setting. Fibroblasts were then stained with trypan blue, to determine number of dead cells. Data were analyzed using ANOVA and t tests. Resilon was similar to gutta-percha and the control. Epiphany was less cytotoxic than Grossman's sealer at both the 1 and 24 h time periods. Epiphany was more cytotoxic than Sealapex at the 1-h time period but less cytotoxic at the 24 h time period. These results indicated that Resilon had a lower cytotoxicity and that Epiphany was more cytotoxic than conventional materials.