Mineral trioxide aggregate (MTA) is considered at the present time as the gold standard for root-end filling in endodontic surgery. However, this biocompatible material presents several drawbacks such as a long setting time and handling difficulties. The aim of this article is to present a new commercialized calcium silicate-based material named Biodentine with physical improved properties compared to MTA in a clinical application. Two endodontic microsurgeries were performed by using specific armamentarium (microsurgical instrumentation, ultrasonic tips) under high-power magnification with an operatory microscope. Biodentine was used as a root-end filling in order to seal the root canal system. The two cases were considered completely healed at 1 year and were followed for one more year. The 2-year follow-up consolidated the previous observation with absence of clinical symptoms and radiographic evidence of regeneration of the periapical tissues.