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The objective of this study was to identify surgical protocols that can improve mucosal healing and postextraction socket closure in patients who underwent radiation therapy for head and neck cancer.The study was designed as a prospective split-mouth trial on 20 patients who needed bilateral paired dental extractions. On the side directly impacted by radiation, chosen to be the study side, the sockets were filled with plasma rich in growth factors (PRGF), whereas, on the other side (control), they were allowed to undergo natural healing.Outcome variables were residual socket volume (RSV), healing index (HI), pain, and postsurgical complications as measured at the 2 sides at the 4 follow-up sessions (up to 30 days after the extraction).Continuous variables were analyzed with Wilcoxon (when matched) or Mann-Whitney (when independent) test; categorical variables, with Chi-squared or Fisher test. Statistical significance was set at P < 0.05. Correlation was estimated with Pearson linear correlation coefficient.The PRGF side showed statistically significant better values for RSV and HI at all checkups and no postoperative complications. The control side had a slower healing and 2 cases of bone exposure, which were successfully cured with PRGF application.The RSV on the 21st day after the extraction was correlated with the dose received but not with the time since radiotherapy.Plasma rich in growth factors proved to be effective in the management of patients with a history of head and neck radiotherapy, accelerating and fostering mucosal healing and avoiding postextraction bone exposures.