Purpose: The present study was aimed to investigate the pre-emptive analgesia attained with oral celecoxib compared with oral acetaminophen post mandibular third molar surgery. Materials and Methods: A double-blinded, randomized, placebo-controlled clinical trial was performed in order to examine patients having a mandibular third molar for extraction under local anesthesia. The patients were randomized for receiving a preoperative oral dosage of celecoxib or acetaminophen as the predictor parameter. The primary outcome parameter was postoperative pain assessed through a visual analog scale (VAS) at different time points. The secondary outcome parameter was the quantity of postoperative analgesics taken in both groups. Statistical analyses included descriptive statistics, the t test, and the Pearson c2 test. Significance was set at P < .05. Results: 60 patients were divided randomly into either celecoxib receiving group or acetaminophen receiving group. The postoperative pain scores in the celecoxib group receiving were significantly lower than those in the acetaminophen receiving group at 4, 6, 8, and 12 hours (P = .078, P = .0012, P = .0211, and P = .011, respectively). The number of patients who didn’t require any analgesics in the celecoxib receiving group was less than that in the acetaminophen receiving group (P =.0186). The average amount of rescue analgesic medication in the celecoxib group (0.6 0.8 dose) was significantly lower than that in the acetaminophen group (1.3 1.0 doses) (P = .002). The Kaplan-Meier curve (KM curve) was indicative of long-term survival of the patients receiving celecoxib compared to those who did not receive any rescue analgesic medication (P = .0055). Conclusions: Celecoxib, as the study reflects, has a significant pre-emptive analgesic effect, thus helpful in reducing the usage of postoperative analgesics after removal of the third molar.