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Introduction: one of the most significant concerns after third molar surgery is the post-surgical dental pain. Regarding the efficacy of the Novafen and Naproxen in pain control treatment, it is important to compare the effect of each of these medications to decide which one should be used. Aim: The aim of this study was to compare the effect of Novafen and Naproxen on pain management in patients after surgical removal of impacted mandibular third molar. Methods and Materials: This study was a clinical trial that was performed as a split mouth and double-blind on 20 patients (12 females and 8 males) with a mean age of (24.2±5.8) which had surgical extraction of impacted mandibular teeth in two different dates. Novafen (Acetaminophen 325mg, Ibuprofen 200mg, and Caffeine 40mg) and Naproxen 500mg were assessed blindly in each date as a pain control treatment. The pain intensity was determined by VAS (Visual Analogue Scale). In this study, data were analyzed based on Mann-whitney U-tests. Results: The mean pain in Novafen group was lower than Naproxen group 4, 8 and 12 hours after surgery (p<0.001). But after 24 hours, pain in both groups were the same and there was no statistically significant difference (p<0.2). Conclusion: The pain in Novafen group was meaningfully lower than Naproxen group hence Novafen can be used as a more effective therapy rather than Naproxen in dental surgeries. Keyword: Naproxen, Novafen, tooth, impacted.