Introduction: Surgical extraction of impacted mandibular third molars frequently leads to postoperative pain, edema, and trismus. In heavy smoking patients, wound healing is further compromised. Platelet-rich fibrin (PRF) is a second-generation autologous platelet concentrate that promotes healing and reduces inflammation. Aim: To evaluate the efficacy of PRF in reducing pain, swelling, trismus, and its effect on bone healing after odontectomy of impacted lower third molars in heavy smoking patients. Materials and Methods: Twenty-eight healthy heavy smoking patients (≥20 cigarettes/day) with bilateral impacted mandibular third molars were included using a split-mouth design. Group I (control): routine extraction with saline irrigation. Group II (study): extraction followed by PRF placement into the socket. PRF was prepared by centrifuging 10 mL venous blood at 3000 rpm for 10 minutes. Postoperative pain (VAS and analgesic count), edema (linear and surface area measurements), trismus (interincisal distance), and bone density (panoramic radiographs with ImageJ software) were evaluated at 2, 7, 30 days, and up to 6 months. Results: The PRF group showed significantly lower pain scores (mean VAS 3.89±0.44 vs. 5.21±0.69, p<0.001) and fewer analgesics used (1.47±0.21 vs. 2.16±0.22 tablets/day, p<0.001). Edema was significantly reduced in the PRF group at 2 and 7 days (average linear measurement 12.38±0.75 vs. 13.14±0.77 cm, p=0.003; surface area 93.4±5.32 vs. 119.4±6.23 cm2, p=0.0045). Trismus was significantly improved (interincisal distance 41.64±10.16 vs. 32.39±12.75 mm at day 2, p=0.043). No significant difference in bone density was found between groups at any time point. Conclusion: PRF effectively reduces postoperative pain, edema, and trismus in heavy smoking patients undergoing impacted third molar surgery, but does not improve bone remodeling.