Background: Impacted mandibular third molar removal is one of the most commonly performed oral surgical procedures. This procedure can lead to several postoperative complications, such as trismus, facial swelling, and pain, which occur as a result of the inflammatory responses to surgery. This study compared the efficiency of preoperative injections of 4 mg versus 8 mg dexamethasone into the pterygomandibular space to reduce postoperative sequelae. Methods: This was a randomized, prospective, split-mouth, controlled study, including 52 mandibular third molar surgeries in 26 patients. Each patient was randomized to either the 4 mg or 8 mg dexamethasone injection group. Dexamethasone was injected into the pterygomandibular space after numbness from local anesthesia.Data were collected for trismus, facial swelling, visual analog scale (VAS) pain score, and the number of analgesics taken during the evaluation period. The level of significance was set at P < 0.05. Results: Statistically significant differences in postoperative facial swelling (P = 0.031, diff = 1.4 mm) and pain (P = 0.012, diff = 0.020) were found between the 8 mg and 4 mg dexamethasone groups. However, there were no significant differences between the groups for trismus and the total number of analgesics consumed (P > 0.05). Conclusion Compared to the 4 mg preoperative dexamethasone injection, the 8 mg preoperative dexamethasone injection into the pterygomandibular space was more effective in reducing postoperative swelling and pain following the surgical removal of the impacted mandibular third molar. However, the difference in trismus could not be evaluated clinically. Therefore, the recommendation of administering the 4 mg dexamethasone preoperative injection is optimal in the third molar surgical procedure.