Aim: This study was performed to compare the sealing ability of Epiphany system, GuttaFlow and Amalgam when used as retrograde filling materialsMethodology: Seventy-two recently extracted permanent, human single canaled teeth with fully formed roots were mechanically prepared using the step back technique after tooth length determination. The canals were then obturated using lateral condensation technique with gutta-percha and AH-26 sealer. The apices of all sample roots were resectioned in perpendicular plane with the long axis of the root for a distance of 3 mm.Root end cavities were prepared 3 mm depth of fissure bur. The samples were then randomly divided into six equal groups of 12 teeth each according to type of retrograde filling material used such that:Group (I): contained 12 samples apically sealed with Epiphany system (Resilon and Epiphany sealer).Group (II): contained 12 samples apically sealed with Epiphany system (Resilon, Epiphany sealer and dentin pre-conditioning).Group (III): contained 12 samples apically sealed with GuttaFlow only.Group (IV): contained 12 samples apically sealed with GuttaFlow and AH-26 sealer.Group (V): contained 12 samples apically sealed with Amalgam only.Group (VI): contained 12 samples apically sealed with Amalgam and Amalgam bond.Each group was further subdivided into two subgroups of 6 samples each according to immersion period in methylene blue such that:Sub-group (i):6 samples immersed for 24 hours.Sub-group (ii):6 samples immersed for 30 days.The dye penetration method was used to test the sealing ability of the different retrograde filling materials.The external surface of each root was covered by two layers of nail polish except at the resected root surface.Each root in the experimental groups and sub-groups was immersed in 2% methylene blue dye in an upright position at room temperature for either of observational periods; 24 hours and 30 days.After the periods of examination had elapsed, the teeth were removed from the dye then washed under running water and left to dry.Each Root was then sectioned longitudinally in a bucco-lingual direction by means of a diamond disc mounted to a slow speed straight hand piece.The longitudinal sections were examined with an optical stereomicroscope at 30X magnification.Results: There was a statistically significant difference between the different materials at the two immersion periods.Also, the results revealed that after 24 hours examination,( group V),Amalgam, showed the statistically significantly highest mean of dye penetration followed by (group VI), Amalgam & Amalgam bond.The statistically significantly lowest mean of dye penetration was found with (group II) Epiphany system (Resilon, Epiphany sealer and Dentin pre-conditioning) then (group I), Epiphany system (resilon, Epiphany sealer only) and (group IV), Guttaflow with AH 26 sealer with no statistically significant difference.Again, the results revealed that after 30 days examination,( group V),Amalgam, showed the statistically significantly highest mean of dye penetration followed by (group VI), Amalgam & Amalgam bond.The statistically significantly lowest mean of dye penetration was found with (group II) Epiphany system (Resilon, Epiphany sealer and Dentin pre-conditioning) then (group I), Epiphany system (resilon, Epiphany sealer only) followed by (group IV), Guttaflow with AH 26 sealer then (group III) Guttaflow.There was a statistically significant difference between the two immersion times; the mean dye penetration after 30 days was statistically significantly higher than dye penetration after 24 hours for any tested material.Conclusion: From this study, it could be concluded that: l. Sealability of Epiphany system (Resilon and Epiphany sealer) could be significantly improved when dentine pre-conditioning is used.2. Amalgam as a root-end filling material has some limitations due to its relative toxicity, delayed expansion, corrosion, potential tissue staining and marginal leakage.3. Application of AH 26 sealer improved significantly the performance of GuttaFlow regarding its sealing ability when used as a retrograde filling material.4. Amalgam as a retrograde should be used in conjunction with an amalgam bond to increase its sealing ability.5. There is no ideal retrograde filling material.