One possible consequence of dentoalveolar trauma is the development of external inflammatory root resorption (EIRR), which represents an anatomic and microbiologic challenge for clinicians. This case report describes different strategies implemented for successful endodontic management of teeth with multiple EIRR lesions, highlighting the orthograde root canal filling using a tricalcium silicate-based material (Biodentine, Septodont, Saint-Maur-des-Fossés, France). A 17-year-old female patient presented with severe pain in the anterior maxillary teeth and a history of trauma. Two- and three-dimensional radiographic exams confirmed EIRR in three teeth, with a total of 11 EIRR lesions, three exhibiting communication with the root canal. Therefore, chemo-mechanical preparation complemented by ultrasonic activation of irrigants and some changes of intra-canal dressing with calcium hydroxide were performed to reduce the microbiologic load of the affected teeth as much as possible. Then, the canals were entirely filled with Biodentine to interrupt the root resorption process and strengthen the remaining root structure. A 60-month follow-up showed the disappearance of bone rarefactions and the complete repair of the 11 EIRR lesions. The favorable long-term response indicates the feasibility of using tricalcium silicate-based putty as part of orthograde endodontic treatment of teeth with EIRR and root perforations.