Medication-related osteonecrosis of the jaw (MRONJ) is a severe side effect of antiresorptive (bisphosphonates and denosumab) and anti-angiogenic therapy used in the management of oncologic and, less frequently, osteoporotic patients. While there is good international agreement on the diagnostic and staging criteria of MRONJ and the cessation of antiresorptive/anti-angiogenic treatments, the gold standard of treatment is still controversial, in particular between non-surgical and surgical approaches.The former usually includes antiseptic mouth rinse, cyclic antibiotic therapy, low-level laser therapy and periodic dental checks; the latter consists of surgical necrotic bone removal. The purpose of this retrospective study was to describe the therapeutic approaches and outcomes of 131 lesions from 106 MRONJ patients treated at the Policlinic of Bari. Non-surgical treatments were chosen for 24 lesions that occurred in 21 patients who, due to comorbidities and/or the impossibility of stopping oncologic therapies, could not undergo surgical treatment. As to the outcome, all the surgically treated lesions (107) showed complete healing, with the exception of 13.5% of the lesions, all of which were stage III, which did not completely heal but showed reduction to stage I. The 24 non-surgically treated lesions never completely healed and, rather, generally remained stable. Only two cases exhibited a reduction in staging.Based on our observations, MRONJ occurring both in neoplastic and non-neoplastic patients benefits more from a surgical treatment approach, whenever deemed possible, as non-surgical treatments do not seem to allow complete healing of the lesions.