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Background: The management of the surgical wound of partially impacted mandibular third molar surgery has a great impact on recovery as well as on food impact retention. The present study used clinical parameters and health-related quality of life (HRQL) to compare outcomes of cyanoacrylate application versus traditional suture of third molar impaction surgery. Methods: This was a retrospective observational study of subjects scheduled for outpatient third molar surgery. Each participant signed an informed consent agreement. Inclusion criteria were as follows: presence of at least one partially impacted mandibular third molar, confirmed with a preoperative panoramic radiograph. Exclusion criteria were the following: smoking, diagnosed diabetes mellitus. Between June 2020 and September 2023, a total of 78 patients of mean age 31.14 years old (range 21–40 years, standard deviation 9.14), were included in this study—38 patients were male, 40 patients were female. A group of patients received traditional silk suture (G1 = 41 patients), while the second group (G2 = 37 patients) received hemostasis performed with fibrin sponge and, after complete soaking of the sponge, the application of cyanoacrylate gel on the blood clot and suture with one 2/0 stitch in order for recovery for secondary closure. The following parameters were measured: HRQL, average pain (AP), maximum pain (MP), complication score (CS), facial swelling (FS), and erythema. Results: For HRQL parameters, oral disability was found to be significantly higher in G1 while AP was significantly higher in G2 (p < 0.05). AP was higher in G2 (p = 0.0098), as well as MP (p = 0.001). No differences were found with regards to CS (p = 0.0759). FS and erythema were higher in G1 (p < 0.0001 for facial swelling, and p = 0.0001 for erythema). Conclusions: on the basis of this study, the use of cyanoacrylate after mandibular third molar surgery appears to be useful in order to reduce postoperative oral disability, facial swelling, and erythema after tooth extraction, with increased average and medium pain: clinicians may consider its use in selected cases. [ABSTRACT FROM AUTHOR]