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The purpose of this study was to compare the microleakage of two root canal sealers, Fibrefill (resin-based sealer) and calciobiotic root canal sealer (CRCS; calcium hydroxide-based sealer), with and without the presence of smear layer. The model used for the measurement of microleakage was a fluid transport model.Sixty human extracted teeth were used in this study. The teeth were divided into four groups and treated as follows. In group A, the smear layer was left intact, and canals were obturated with gutta-percha and Fibrefill. In group B, the smear layer was removed, and canals were obturated with gutta-percha and Fibrefill. In group C, the smear layer was left intact, and the canals were obturated with gutta-percha and CRCS. In group D, the smear layer was removed, and canals were obturated with gutta-percha and CRCS. Microleakage was measured at 7 days, 1 month, and 2 months.The results showed that the Fibrefill groups with and without smear layer leaked significantly less than the CRCS groups at all experimental times. No significant difference was found between the groups of same materials, but the microleakage values were less when the smear layer was removed.