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Background/Objectives: Glucocorticoids are drugs that are increasingly used in oral surgery to reduce trismus, inflammation, and postoperative pain, three frequent complications after the surgical extraction of impacted lower third molars. The aim of this study was to compare the effect of 8 mg dexamethasone versus 40 mg methylprednisolone in the prevention of postoperative complications after third molar surgery. Methods: A randomized double-blind clinical trial was conducted following CONSORT guidelines. In detail, 84 patients were included in the study, who randomly received a single preoperative submucosal dose of dexamethasone (8 mg) or methylprednisolone (40 mg). The variables analyzed, as primary outcomes, were trismus, inflammation, and postoperative pain. The measurements were performed at baseline (0 h), 3 h, 7 h, 24 h, 48 h, and 7 th day using a Visual Analog Scale (VAS), Verbal Rating Scale (VRS), and the Gabka–Matsumara method. Results: Dexamethasone reduced trismus, inflammation, and postoperative pain significantly better than methylprednisolone. Conclusions: Preoperative submucosal administration of 8 mg dexamethasone is effective and safe in reducing the severity of postoperative complications following surgical extraction of impacted lower third molars. [ABSTRACT FROM AUTHOR]