Aim: To compare the bond strength, sealing ability and biocompatibility of iRoot SP sealer, Activ GP system and AH Plus sealer.Methodology: Ninety single rooted permanent extracted teeth were decoronated and chemomechanically prepared by a crown down technique using k3 rotary system till size # 40. Teeth were divided into 6 groups of 15 teeth each according to the obturation material and technique. Group 1 (iRoot SP sealer and gutta percha /single cone technique), group 2(iRoot SP sealer and gutta / multiple cones technique), group 3(Activ GP point and Activ GP sealer/ single cone technique), group 4(Activ GP point and Activ GP sealer /multiple cones technique), group 5(AH Plus sealer and gutta percha / single cone technique and group 6(AH Plus sealer and gutta percha /multiple cones technique). Thirty teeth (5 teeth from each group) were used to measure the bond strength of the previously mentioned obturating materials with a push out universal-testing machine. Another sixty teeth were used for the apical sealing ability test (10 teeth from each group).Five samples were tested at 1 week period and another 5 samples were tested at 4 weeks period for each group. Microleakage was measured using the linear dye penetration using the clearing technique and leakage assessment was done using a stereomicroscope. In the biocompatibility study, ten male albino Western rats were used. The tested sealers were prepared and loaded in clean, sterile polyethylene tubes while; the butt end of the Activ GP point was cut into segments of 10 mm. The tubes containing the freshly mixed sealers as well as the Activ GP point were placed carefully in the pouches made on the dorsal surface of the rats. The implants were kept in place for either 1 week or 4 weeks before animals’ scarification. Results: iRoot SP and AH Plus sealers recorded the highest mean push out bond strength values. Both were statistically significant different from Activ GP . There was no statistically significant difference between AH Plus and iRoot SP. The mean leakage value of iRoot SP sealer was statistically significant lower than AH Plus and Activ GP sealers. No statistically significant difference between AH Plus and Activ GP sealers in the mean leakage values. At 1week, there was no statistically significant difference in inflammation scores between the four tested materials. At 4 weeks period, Activ GP sealer recorded the statistically significant highest mean value with no statistically significant difference between other tested materials. For the edema, hemorrhage and the coagulative necrosis, at 1 week and 4 weeks, no statistically significant difference between the tested materials. At 4 weeks period, there was a statistically significant decrease in edema score in AH Plus sealer. Only one specimen showed presence of capsule which was Activ GP point at 4 weeks.Conclusion: The newly introduced calcium phosphate based sealer iRoot SP had comparable bond strength, biocompatibility and superior sealing ability than AH Plus sealer. Activ GP system had lower bond strength, sealing ability and biocompatibility than iRoot SP sealer.