The objective of this study was to compare the pre-emptive analgesic effect of rofecoxib, a cyclooxygenase (COX)-2 inhibitor, with a more traditional and commonly used analgesic, ibuprofen, for mandibular third molar surgery, utilizing a prospective, randomized, double-blind, placebo-controlled clinical trial. Fifty-five healthy patients who were scheduled to undergo surgical removal of an impacted mandibular third molar as outpatients at one of two government dental clinics in Fiji were enrolled. The patients were divided randomly into three groups to receive 50 mg rofecoxib or 400 mg ibuprofen, or a placebo 1 h prior to surgery. A dose of 1000 mg paracetamol was offered as rescue medication. Participants recorded their pain intensity on a 10-cm visual analogue scale 1 h before and just prior to surgery and every 30 min for 6 h following surgery. There were no significant analgesic differences between rofecoxib and ibuprofen at any time intervals postoperatively. Ibuprofen was significantly better at reducing pain at all time intervals by comparison with the placebo. Rofecoxib provided significantly better pain relief compared with the placebo, except at 60, 180, and 240 min postoperatively. Rescue medication use was significantly lower in the rofecoxib and ibuprofen groups by comparison with the placebo group; however, there was no significant difference between the two therapeutic groups. Rescue medication was used by 50%, 25%, and 94% of patients receiving rofecoxib, ibuprofen, and placebo, respectively. Ibuprofen, a commonly used over-the-counter analgesic, is as effective as rofecoxib for the relief of acute postoperative pain following third molar surgery when used pre-emptively.