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The pulp and the periodontium are invariably anatomically and functionally related to each other. Lesions involving both the periodontium and the pulp complicate diagnosis, treatment planning and prognosis. An emerging approach to periodontal therapy is the concept of regeneration. In this case report, a novel combination therapy of a blend of platelet rich fibrin with bone graft and guided tissue regeneration membrane was used in the treatment of a perio-endo lesion of a multirooted tooth. A successful outcome in alleviating patient’s symptoms and regeneration was seen.