Purpose Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is a well-recognized pathologic entity that is challenging and difficult to manage. Recent literature contains several articles, with most recommending conservative management. This report describes a treatment modality for advanced cases of BRONJ that involves bone resection and autologous platelet-rich plasma (PRP). Patients and Methods This case series consisted of 25 patients with BRONJ lesions and a history of intravenous bisphosphonate therapy for metastatic bone diseases that did not respond to conservative treatment. All patients were surgically managed by a standardized protocol combining bone resection and PRP. Results Of the 25 patients, 20 (80%) showed complete wound healing during follow-up. Median follow-up was 36 months. Microscopic examination showed actinomyces in 15 specimens. Conclusion BRONJ has been shown to be refractory to conservative management. Treatment of refractory BRONJ with a combination of bone resection and PRP was found to be an effective therapy in most patients and should be considered an alternative treatment modality for management of advanced cases.