ObjectiveThis study aimed to summarize the clinical outcomes of surgical treatment for severe medication-related osteonecrosis of the jaw (MRONJ, stages 2 and 3).MethodsA retrospective cohort study was conducted to review the patients with severe MRONJ from July 2013 to May 2021. All patients were treated surgically. The characteristics and clinical variables were recorded and analyzed.ResultsA total of 104 patients (123 MRONJ lesions) were included, including 42 males and 62 females, aged 64.6±9.1 years. The primary disease was malignant in 91 cases and benign in 13 cases. Forty-three cases (35.0%) were stage 2 lesions, and 80 (65.0%) were stage 3 lesions. Thirty-nine (31.7%) lesions were located in the maxilla, and 84 (68.3%) lesions were located in the mandible. The most commonly used bisphosphonates were zoledronic acid (n=89; 85.6%), followed by alendronate (n=10; 9.6%), and pamidronate (n=10; 9.6%). Antiangiogenic agents were administered in 62 (59.6%) patients. The mean duration of bisphosphonate therapy was 34.7±25.8 months, and the mean duration of drug holiday was 10.1±10.7 months. All operations were performed under general anesthesia. For stage 2 lesions, debridement and saucerization were performed to completely resect the lesions, and the wounds were closed without tension through local mucoperiosteum flaps. For stage 3 lesions, after the lesions were completely resected, the bone defect was covered by reconstruction plate fixation and ipsilateral submandibular gland translocation, iodoform gauze, and buccal fat pad accordingly. The follow-up period ranged from 3 months to 6 years; 81.3% (100/123) of the lesions reached mucosal healing at the last follow-up, whereas wound infection and dehiscence occurred in 18.7% (23/123) of the lesions postoperatively.ConclusionSevere MRONJ lesions could be surgically treated to achieve mucosal healing. Vascularized flap reconstruction could be considered if the patient’s general condition could tolerate it.