The final restoration is an important factor in successful root canal treatment. Inadequate final restoration leads to bacterial and salivary penetration in the root canal, causing a treatment failure. Placement of the orifice barrier under the final restoration could reduce saliva and bacterial contamination in the root canal. This study aimed to determine the differences in microleakage between Smart Dentin Replacement, Glass Ionomer Cement and Flowable Resin Composite as orifice barrier in root canal treated teeth. The design of this study was laboratory experimental. The sample was 27 premolars teeth with 1 or 2 mandibular permanent teeth that had been extracted and divided into 3 groups: Smart Dentin Replacement, Glass Ionomer Cement and Flowable Resin Composite. Teeth were prepared by crown-down method and obturated with gutta-percha and AH Plus. After placement of the orifice barrier with the thickness of 4 mm, the teeth were immersed in 2% methylene blue solution at 37ºC for 24 hours. Teeth sectioned in buccolingual direction and observation of microleakage using stereomicroscope at 10x magnification. One-Way ANOVA results showed p = 0,000 (p <0.05) which means there were microleakage differences between Smart Dentin Replacement, Glass Ionomer Cement and Flowable Resin Composite. Tukey Post Hoc results showed significantly different glass ionomer cement (p <0.05) compared to Smart Dentin Replacement and flowable resin composite. Smart Dentin Replacement has the smallest microleakage value of 1.70, but does not differ significantly with flowable composite resin.