Objective: An ideal root filling materials must have the ability to seal the root canal system in three dimensions, be nontoxic and well tolerated by periradicular tissues, have dimensional stability, nonabsorbability, and not affected by the presence of moisture. MTA has good biological properties, and it is a mineralization-inducing materials with different applications in endodontics. But owing to its physical properties, this materials is not recommended as a root canal sealer. However, a resin sealer based on mineral trioxide aggregate (MTA Fillapex) was recently produced with this indication. Because sealers are in contact with the periodontal tissues, it is important to know their cytotoxic effects. So the purpose of this study was to evaluate the cytotoxicity of MTA canal sealer (MTA Fillapex) compared with Angelus MTA cement and AH26 Materials and Methods: Human periodontal ligament fibroblast cells (HPLF) were cultured in media previously exposed to MTA Fillapex, Angelus MTA cement and AH26 for 24 hours to 1week. Cytotoxicity was evaluated by methol-thiazol-diphenyl tetrazolium (MTT) assay in spectrophotometer to check cell survival and viability rate. Results: Cell viability remained above 50% in Angelus MTA group after 24 hours and declined after 48 hours and1week. AH26 induced an intermediate cytotoxicity in 24 hours but the cytotoxicity remained unchanged after 48 hours and 1week. MTA Fillapex was less toxic than AH26 after 24 hours but the toxicity of both materials was the same at 48 hours and 1week. Conclusion: This study showed that angelus MTA is less toxic in comparison with MTA Fillapex sealler and AH26.