This study aimed to compare between I Root BP and MTA regarding apical sealing ability, marginal adaptation, biocompatibility and clinical performance. Seventy extracted teeth were resected; retrograde cavities were prepared and divided into 2 groups according to the retrograde filling material used. Dye extraction method was used to evaluate the sealing ability. Twelve male adult New Zealand rabbits were used to test the intraossous biocompatibility of the 2 materials. Three holes were drilled in the right and left femurs; MTA and I Root BP were prepared and inserted into the holes leaving the third hole empty as a control. Animals were sacrificed. Specimens were prepared for histopathological evaluation. In the clinical study, 20 patients undergo endodontic surgery were divided into 2 groups according to the retrograde filling material used. Each patient was subjected to clinical and radiographic evaluation by cone beam CT. I Root BP can be recommended as retrograde filling material since it showed apical sealing, biocompatibility and clinical performance comparable to MTA.