The analgesic efficacy of the cyclooxygenase-2 specific inhibitors, valdecoxib and rofecoxib, were evaluated in patients following oral surgery. In a randomized, double-blind, controlled trial, patients experiencing moderate or severe pain received single-dose valdecoxib 40 mg (n=99), rofecoxib 50 mg (n=101), or placebo (n=50) within 4 hours after multiple third molar extraction with bone removal. Onset of action was significantly faster with valdecoxib 40 mg (30 minutes) compared with rofecoxib 50 mg (45 minutes), as measured by pain intensity difference and pain relief scores (P <or= 0.05). Valdecoxib and rofecoxib provided a similar magnitude of analgesic effect, as measured by time-weighted sum of total pain relief, at 6 hours post dosing. However, valdecoxib was significantly superior to rofecoxib with respect to mean time-specific pain intensity difference and pain relief scores from 30 minutes to 1.5 hours post dose (P < 0.05). All treatments were well tolerated.