Abstract Objectives: Third molar surgeries are a routine procedure in oral and maxillofacial surgery and its associated pain is bothersome to patients. The purpose of this study was to compare the analgesic effect of Gelofen and naproxen in lower third molar surgery. Materials and Methods: A single-blinded randomized clinical trial was designed, and patients were randomly allocated into four groups (n = 20 cases in each group): pre-Gelofen group: 400 mg Gelofen 30 min preoperative and continuing every 6 h, Gelofen group: 400 mg Gelofen immediately postoperative and continuing every 6 h, pre-naproxen group: 500 mg naproxen 30 min preoperative and every 8 h, and naproxen group: 500 mg naproxen immediately postoperative and every 8 h. The pain intensity was recorded using the visual analog scale at 2, 6, 12, and 24 h after surgery. Results: Pain intensity decreased in a linear pattern in all groups after 2, 6, 12, and 24 h. In pre-naproxen group, pain decreased suddenly between 2 and 6 h, but after 6 h, pain relief was slower than other groups. The mean pain intensity at 2 h postoperative for the pre-naproxen group was significantly lower than Gelofen group, and at 6 h, it was less than all other groups. At 12 and 24 h after surgery, pain intensity in all groups was similar except for the Gelofen group. Conclusion: Under limitation of the present study, preoperative intake of naproxen showed more effective pain relief than other groups.