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The purpose of this prospective, double-blind, randomized clinical trial was to evaluate the postoperative healing of endodontic periapical microsurgery after local administration of dexamethasone.Sixty patients were divided into 2 groups. The dexamethasone group received a single local submucosal injection of 4 mg dexamethasone, and the placebo group received a submucosal injection of saline solution at the conclusion of standardized periapical microsurgery. Acetaminophen and hydrocodone/acetaminophen were prescribed for pain relief. A Likert-like 6-point scale was used for self-evaluation of pain, bruising, swelling, and wound healing at 24, 48, 72, 96 hours and at 1 week. The number of tablets taken was registered. Data were analyzed using the chi-square and Fisher exact tests at a significance level of P < .05.No improvements in pain, bruising, and wound healing were registered at any time interval. No difference was found in the number of tablets taken for pain relief. Subjects who received the dexamethasone injection reported less swelling 24 hours after periapical microsurgery (P < .05) but showed no significant benefit for the longer follow-up periods.This study shows that a 4-mg dose of dexamethasone administered through a local submucosal injection after periapical microsurgery has minimal impact on pain, bruising, and apparent wound healing at any time over a 7-day interval, and the impact on swelling seems limited.Periapical surgery is regarded as an integral part of modern endodontics, and pain, swelling, and bruising have long been inevitable consequences of endodontic surgery.The anti-inflammatory efficacy of corticosteroids has led to their use after periodontal surgery and removal of impacted third molar teeth.The effects of submucosal injection of 4 mg dexamethasone postoperatively in apical microsurgery are still unknown.