Mandibular third molar surgery is commonly associated with postoperative pain, swelling, and trismus. Platelet-rich fibrin (PRF) has been proposed as a biological adjunct to improve postoperative healing; however, its effectiveness in smokers remains unclear. This prospective randomized split-mouth clinical study aimed to evaluate the effects of PRF on postoperative pain, swelling, trismus, and analgesic consumption after impacted mandibular third molar surgery in smokers and nonsmokers. Thirty patients with bilaterally impacted mandibular third molars were included. PRF was placed in one extraction socket, while the contralateral socket served as the control site. Postoperative clinical outcomes were assessed during the first postoperative week and compared between smoking and nonsmoking patients.