The aim of this study was to compare the effect of using L-PRF in patients undergoing impacted lower third molar surgery with either primary or secondary closure techniques. Methods: This prospective, randomized, double-blind, split-mouth clinical trial was conducted on patients with bilateral impacted lower third molars of a similar position. Primary closure was performed in group 1 and secondary closure in group 2. The group 1 closure technique was applied to one side of the patients, and the group 2 closure technique was applied to the other side at different times. Of the 45 patients evaluated, 9 patients were excluded from the study because of alveolitis and failure to attend regular control visits out. Results: Of the 36 patients included in the study, 23 were female and 13 were male, with a mean age of 22.42 ± 3.36 years. The secondary closure group had lower VAS scores at hour 6 (p < 0.05). Pain decreased more in the primary closure group when comparing changes between the VAS scores at 6 hours and 7 days (p < 0.05). Conclusions: The results of this study, showing that both secondary and primary closure are effective, with similar outcomes in terms of pain, swelling, and trismus, should be supported by future clinical trials.