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ImportanceProton radiation therapy (PRT) has reduced radiation-induced toxic effects, such as mucositis and xerostomia, over conventional photon radiation therapy, leading to significantly improved quality of life in patients with head and neck cancers. However, the prevalence of osteoradionecrosis (ORN) of the jaw following PRT in these patients is less clear.ObjectiveTo report the prevalence and clinical characteristics of ORN in patients with oral and oropharyngeal cancer (OOPC) treated with PRT.Design, Setting, and ParticipantsThis case series reports a single-institution experience (Memorial Sloan Kettering Cancer Center, New York, New York) between November 2013 and September 2019 and included 122 radiation therapy–naive patients with OOPC treated with PRT. Data were analyzed from 2013 to 2019.Main Outcomes and MeasuresClinical parameters, including sex, age, comorbidities, tumor histology, concurrent chemotherapy, smoking, comorbidities, and preradiation dental evaluation, were obtained from the medical record. Patients with clinical or radiographic signs of ORN were identified and graded using the adopted modified Glanzmann and Grätz grading system. Characteristics of ORN, such as location, clinical presentation, initial stage at diagnosis, etiology, time to diagnosis, management, and clinical outcome at the last follow-up, were also collected.ResultsOf the 122 patients (mean [SD] age, 63 [13] years; 45 [36.9%] women and 77 [63.1%] men) included in this study, 13 (10.6%) developed ORN following PRT during a median (range) follow-up time of 40.6 (Conclusions and RelevanceIn this case series, the prevalence of ORN following PRT was found to be 10.6%, indicating that ORN remains a clinical challenge even in the era of highly conformal PRT. Clinicians treating patients with OOPC with PRT should be mindful of this complication.