© 2021 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-FacialIntroduction: Increased incidence of localized osteonecrosis in the jaw bones caused by bisphosphanate use and reduced quality of life of the patients led researchers to diagnose the disease in the early period and to investigate the effective treatment modality. Objective: Treatment of medication-related osteonecrosis of the jaw patients is based on individual protocols from clinical experience, as there are no definitive treatment guidelines. In view of the lack of consensus on the effectiveness of medication-related osteonecrosis of the jaw treatments in the literature, the aim of this study was to evaluate the surgical technique described in the treatment of advanced stages of medication-related osteonecrosis of the jaw patients. Methods: Twenty-one patients affected by Stage 2–3 medication-related osteonecrosis of the jaw were treated with ultrasonic piezoelectric bone surgery for necrotic bone removing, leukocyte and platelet-rich fibrin concentrate obtained from the patient's peripheral blood and Nd:YAG laser for biostimulation. Success was assessed as the maintenance of full mucosal coverage without signs of residual infection at 1-month (T1), 3-months (T2), 6-months (T3) and 1-year (T4) after surgery. Logistic regressions were used to evaluate the association between the different independent variables and treatment outcomes. Results: Two Stage 3 patients had delayed healing at 1 month after the operation. Complete mucosal healing was achieved in all patients at the third month. Multivariate analysis demonstrated that different variables were not significantly correlated with delayed healing (p > 0.05). Conclusion: The surgical protocol presented in this study shows promising results for surgical management of advanced stages of medication-related osteonecrosis of the jaw patients.