Background. The aim of this study was to compare retrospectively the effect of three different treatment protocols on the healing outcome in patients with established medication-related osteonecrosis of the jaw (MRONJ). Methods. A total of 34 MRONJ patients were recruited from the Department database and were divided according to the treatment protocols in a study group (G1) and two control groups (G2 and G3). G1 was treated with antibiotic therapy, surgery, leukocyte- and platelet-rich fibrin (L-PRF), and photobiomodulation; G2 was treated with antibiotic therapy and surgery; G3 was treated with antibiotic therapy and photobiomodulation. Various clinical variables and treatment protocols were analyzed to determine their correlation with the healing outcome at three and six months of follow-up. Results. There was a significant association between the different treatment protocols and the outcomes at both three and six months follow-up (p = 0.001 and p = 0.002, respectively). No significant association was observed between the outcomes and MRONJ localization, MRONJ stage, duration of drug treatment, gender, diabetes, corticosteroid therapy, smoking habits, underlying disease, and history of chemotherapy at both three and six months follow-up. Conclusions. Our results show that the combination of antibiotic therapy, surgery, L-PRF, and photobiomodulation may effectively contribute to MRONJ management.