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Objectives: This study investigated and compared the effectiveness of a phytotherapeutic drug composed of herbal extracts on postsurgical discomfort after mandibular third molar surgery. Materials and methods: Eighty-two patients requiring the surgical removal of a mandibular third molar were randomly assigned to receive placebo (group 1), ibuprofen (group 2), and a phytotherapeutic drug (composed of baicalin, 190 mg; bromelain, 50 mg; escin, 30 mg) (group 3). Drugs were administered after tooth extraction twice a day for 5 days. The primary outcome, pain, was evaluated using a visual analogue scale at 2 h, 6 h, 12 h, 24 h, 48 h, and 7 and 10 days after surgery. The secondary outcomes were the changes in maximum mouth opening and facial contours (mm) between baseline and at 24 h, 72 h, and 7 and 10 days after surgery. Results: Compared to the baseline, all treatments demonstrated an improvement in the primary and secondary outcomes. Moreover, compared to groups 1 and 2, patients in group 3 yielded a significant reduction of the postoperative pain score at 12 h (p < 0.001), 24 h (p = 0.010), and 48 h (p = 0.048) after surgery. The mean reduction of the swelling and trismus was similar between groups. Conclusions: The results of this study suggest that a postoperative administration of a phytotherapeutic drug was found to be effective in postoperative pain management after the surgical removal of impacted mandibular third molars. Clinical relevance: The phytotherapeutic drug composed of herbal extract determined a decrease in the severity of postoperative pain compared to ibuprofen and placebo. [ABSTRACT FROM AUTHOR]