The pre-emptive efficacy of etoricoxib has reduced immediate postoperative pain in impacted third molar surgery; however, data comparing pre- and post-operative administration is lacking. The objective of this split-mouth, double-blind, randomized–controlled clinical trial was to assess and compare the efficacy of preoperative versus postoperative administrations of single-dose etoricoxib 120 mg for the management of acute postoperative pain in mandibular impacted third molar surgery. A total of 31 patients were included in this study. Each patient underwent two operations of bilaterally symmetrical third molar surgery based on allocation assigned by simple randomization technique into experimental (Preoperative administration: etoricoxib 120 mg) and control (Postoperative administration: etoricoxib 120mg) groups with washout period of one month. The postoperative assessment of pain was performed by using the 11-point Numerical Rating Scale (NRS) for two days and the total rescue analgesic requirement for seven days. The average pain scores and total analgesics rescue analgesics were compared by using Wilcoxon signed-rank test. P-value <0.05 was considered a significant difference. The preoperative administration of etoricoxib resulted in lower mean pain scores at 4, 6, 8, 12, 16, 20, and 48 hours after surgery when compared with the control group with a significant difference (p<0.05). The mean value of the total rescue analgesic requirement was not significant between the experimental and control groups (p>0.05). The preoperative administration of etoricoxib 120 mg revealed a significant difference in pain when compared to the same amount of drug administered postoperatively after four hours of local anesthesia deposition in mandibular third molar surgery. The mean rescue analgesic requirement was not statistically significant between both groups in the postoperative evaluation period.