Surgical removal of impacted mandibular third molars constitutes one of the most frequently performed procedures within oral surgery. This surgery procedure is associated with many post-operative complications. Advanced platelet-rich fibrin (A-PRF) belongs to the second generation of platelet concentrates and is rich in numerous growth factors. The aim of this study was to assess the influence of A-PRF on selected clinical features following the surgical removal of impacted mandibular third molars. The research was conducted on 100 generally healthy patients, who underwent a lower third molar odontectomy in Department of Oral Surgery, Medical University of Gdańsk, Poland, between 2018 and 2019. The research group consisted of 50 patients (immediate A-PRF socket filling) and control group (50 patients without A-PRF socket filling). During the study, the following clinical features were assessed: pain (visual analog scale), analgesics intake, the presence of trismus, edema, hematomas within the surrounding tissues (e.g., cheek), prevalence of pyrexia, dry socket, secondary bleeding, presence of hematomas, skin warmth in the post-operative area, and bleeding time observed by the patient were analyzed on the 3rd, 7th, and 14th day after the procedure. There was a significant association between A-PRF socket filling and pain intensity, the analgesics intake, trismus, and edema on the 3rd and the 7th day (p < 0.05). The presence of hematomas and skin warmth on the 3rd day after the surgery (p < 0.05) were also statistically associated with A-PRF use. The study showed that in reducing the incidence of postoperative complications, A-PRF was more important than the position of the tooth or the duration of the procedure. The growth factors in A-PRF reduce postoperative complications, such as pain, trismus, edema, analgesics intake, presence of hematomas, and skin warmth, after mandibular wisdom teeth odontectomy.