Aim: The objective of this study was to compare the efficacy of different doses of pregabalin and intravenous ibuprofen with regard to pain management and analgesic consumption after third molar surgery. Materials and Methods: Ninety patients who had been scheduled for third molar surgery were assigned to four different treatment groups. The inclusion criteria consisted of the presence of fully or partially bony retentive asymptomatic mandibular third molars. These groups are included the following: (Group 1) premedicated with oral placebo and intravenous (IV) placebo, (Group 2) premedicated with oral placebo and 400-mg IV Ibuprofen, (Group 3) premedicated with 75-mg oral pregabalin and 400-mg IV ibuprofen, and (Group 4) premedicated with 150-mg oral pregabalin and 400 mg IV ibuprofen. Postoperative pain was assessed with visual analog scale (VAS) every hour for the first 12 hs following the surgery. Pain was then assessed at different time intervals during 7 days following the surgery. KruskaluWallis tests were used to compare the four groups in terms of VAS pain scores, analgesic consumption, and first rescue analgesic request time after the surgery. Results: At the end of the study, the results of 80 patients (20 patients per group) were analyzed. The group 4 had lower pain intensity compared with other groups at various time intervals. This difference is statistically significant in between the first 3u10 h (first day) and single-time intervals in second, third, fifth, and sixth postoperative days. Postoperative analgesic consumption was not statistically different between the groups. The first rescue analgesic request time after surgery was different between the pregabalin combination groups and group 2. No significant difference in the side effects was observed. Conclusion: These findings suggest that preoperative coadministration of 150-mg pregabalin and IV ibuprofen may be useful in improving pain control after third molar surgery.