Because of increased attention focused on administering dexamethasone to treat third molar surgical complications, this study investigated the efficacy of single-dose dexamethasone in managing postoperative complications after impacted third molar surgery. Pain intensity and analgesic intake, patients' discomfort, limitation of oral function, and limitation of daily activities were assessed.This triple-blinded split-mouth randomized controlled clinical trial included patients 18 to 30 years old who underwent randomized bilateral extractions of impacted mandibular third molars during 2 consecutive sessions. Each patient was given a single-dose intramuscular injection of dexamethasone (0.1 mg/kg) preoperatively in 1 session and a placebo in the other session. Data were collected daily for 7 postoperative days, and 14 patient-centered outcomes were interpreted. A 2-tailed P value less than .05 was considered significant.All 32 patients (100%) enrolled completed the study. When administered dexamethasone, patients reported less pain (P ≤ .007), took fewer analgesics (P ≤ .002), reported less swelling (P ≤ .007), had less difficulty in eating (P ≤ .024), had less difficulty in enjoying food (P ≤ .005), had less difficulty in speech (P = .043), had less trismus (P = .005), were absent less from school or work (P ≤ .016), and had less disruption of daily activity (P ≤ .042). The differences between the 2 conditions in bleeding, malaise, and sleep disturbance were not significant (P > .05).Prophylactic dexamethasone administered intramuscularly before third molar surgery should be recommended as a safe and effective strategy for decreasing pain and discomfort and enhancing oral functions and daily activities, unless contraindicated.