BACKGROUND: Recently, new calcium silicate bioceramic sealers were introduced to the market. The selection of root canal sealers should not only be based on the different physical parameters but also on local biocompatibility and tissue tolerance.
 AIM: This study aimed to evaluate and compare the in-vivo biocompatibility of a BioRoot RCS in parallel to MTA Fillapex and AH Plus sealers.
 METHODS: Polyethylene tubes containing the freshly mixed test materials were implanted in the subcutaneous tissue of 32 Wistar rats. Empty tubes served as negative controls. After 7, 14, 30, and 60 days, the animals were sacrificed, and the implants with surrounding tissues were processed for routine histological analysis. Histological sections were analyzed under light microscopy. The tissue response was determined by the inflammatory cell infiltration intensity and the fibrous capsule thickness.
 RESULTS: Results revealed a statistically significant decrease of the inflammation intensity by time within each group for all tested sealers and control. A well-defined thin capsule was observed for all tested sealers at 60 days.
 CONCLUSION: BioRoot RCS exhibited rapid recovery of inflammation similar to controls. Thus, within the limitations of this study, it can be considered a biocompatible sealer with acceptable tissue tolerance.