Abstract: This systematic review aimed to determine whether the pentoxifylline and tocopherol (PENTO) protocol effectively reduce the risk of osteoradionecrosis (ORN) in patients undergoing tooth extraction after head and neck radiotherapy. We searched PubMed, SCOPUS, LILACS, EMBASE, Web of Science, and Cochrane databases up to August 2022. We considered only studies that included patients diagnosed with head and neck cancer undergoing tooth extraction with PENTO prophylaxis after radiotherapy. Of the 642 studies identified, 4 were included. Across the included studies, 387 patients had 1871 teeth extracted while on PENTO prophylaxis. The interval of the PENTO protocol differed among the studies included. Overall, a total of 12 (3.1%) patients had ORN, whereas at the individual tooth level analysis the ORN rate was 0.9%. Insufficient evidence exists to promote using the PENTO protocol before dental extractions to prevent ORN Ver menos