Introduction: The main objective of endodontic treatment is the total debridment and obliteration of root canal space. Thus, the development of tight seal at apical foramen against microbes and bacteria that might be introduced in the pulp is a major concern. Also the coronal seal is as important as the apical seal. So efforts have been made on developing materials and techniques for obturating and sealing the radicular space.Materials used for obturation consists of a core filling material binded together with sealer to fill irregularities and spaces between the core material and dentin walls. This would create two interfaces, core/sealer interface and sealer/dentin interface decreasing the possibilities of proper sealing.The most popular materials are gutta percha core material. It is used with different sealer types as ZnO and Eugenol, calcuim hydroxide or silicon based sealers. One of the recently developed sealers is the resin based sealers, aiming for adhesion with root canal walls. The resin based sealer AH plus is one of the recently introduced epoxy based sealers with good adhesive properties to the dentin wall, but the main disadvantage of Gutta percha that it doesn’t adhere to this sealer that might be a cause of improper seal inside the root canal.So in attempt to provide a better seal, new adhesive technologies were introduced in the types of core/sealer system. EndoRez system was one of these systems. It consists of a resin coated gutta percha point that binds with EndoRez sealer to create monoblock in the canal space. EndoRez is a Urthane methacrylate resin-based sealer with hydrophilic properties that improve sealing ability even in moist canals.Recently, a thermoplastic synthetic resin core material, the resilonwas introduced. It aimed to create an adhesive bond to the resin sealer, the Realseal (a methacrylate based sealer) that adheres to canal wall, forming the monoblock.They are both claimed to be biocompatible and have similar properties to Gutta percha with better adhesion and sealing ability. Such claims needs further investigations.Aim of study: Comparative study of cytotoxicity and sealing ability of three resin –based root canal sealers.Cytotoxicity test was performed with tissue culture method on fibroblast cell using MTT assays at different time periods 24 hours, 72 hours and 7 days.Material and Methods: Sealing ability test was done using bacterial leakage model (E.faecalis the most commen in root canal) . Fifty teeth was divided into 5 groups , 10 teeth for each group (n=10).Teeth were decoronated, prepared using crown – down technique . group 1 was obturated with Realseal with resilon points , group 2 was obturated with AHplus and gutta-percha, group3 was obturated with Endorez and Endorez points, group 4 was obturated with Endorez and resilon points, group 5 was obturated with Endorez and gutta-percha. Obturation was done using lateral condensation technique. Two teeth from each group was observed under scanning electron microscope.Results: The results showed that Endorez sealer was the most toxic followed by AH plus sealer then Realseal sealer is the least toxic while group 3 Endorez with Endorez points have the best seal followed by group2 of AH plus sealer and gutta percha then group1 of realseal sealer and Resilon points while group 4 and 5 have the least sealing ability. It was concluded that Endorez sealer with Endorez points have better apical seal but it was the most toxic.