Objective: The study aimed to assess the effect of topical applications of an amino acid and sodium hyaluronate gel after mandibular third molar extraction. Method and Materials: 136 patients requiring mandibular third molar extraction were enrolled. An amino acid and sodium hyaluronate gel was applied to the sockets of patients in the test group immediately following the extraction. The sockets of controls were simply flushed with a sterile saline solution. Patients' outcomes and postoperative complications were assessed 7 and 14 days after surgery. The cumulative incidence of dehiscence and secondary outcome measures were analyzed using a chi-square test. Results: Concerning the primary outcome, the incidence of dehiscence was 27.4% after 7 days in the treatment group and 36.4% in the controls (P = .28), and at 14 days it was 21.4% and 36.0%, respectively (P = .10). No statistically significant differences emerged in other variables (mouth opening range, appearance of soft tissue, presence of pus, pain on palpation of the alveolar socket, alveolitis, local lymphadenopathy, and adverse reactions). Pain perception was always lower in the treatment group during the first 7 days after surgery. Conclusion: Topical applications of an amino acid and sodium hyaluronate gel after mandibular third molar extraction made no statistically significant difference to the variables examined in the test and control groups. Clinical Relevance: This trial focused on postoperative complications after surgical third molar extraction. The use of a gel containing amino acid and sodium hyaluronate was investigated for the management of postoperative pain, edema, alveolitis, wound dehiscence and swelling. Keywords: extraction, hyaluronic acid, oral surgery, oral surgical procedures, pain, wound healing