This study explored the effects of L-PRF on pain, soft tissue healing, periodontal condition, and post-extraction bone repair of mandibular third molars (3Ms). A randomized, prospective, triple-blind, split-mouth clinical trial was conducted with 34 volunteers. Eligible patients were randomly allocated into two treatments: G1 (without L-PRF), G2 (alveoli filled with L-PRF), in which the removal of bilateral 3Ms was performed at the same surgical time. Outcomes were assessed according to a visual analogue scale (pain), soft tissue scoring system (wound healing), periodontal probing of mandibular second molar. Bone repair was determined by volumetric analysis (ITK-SNAP software) and fractal analysis (ImageJ software). An intention-to-treat approach to Statistical analysis was used. L-PRF reduced pain in the 7-day postoperative follow-up (p = 0.019) and not only improved soft tissue healing after 1 month of follow-up (p = 0.021), but also probing depth (distal face) in 3 months postoperatively (p = 0.011). Significant alveolar reduction occurred in 3 months after surgery in both treatments (p < 0.05), however, this was more significant in G1 (p = 0.016). The fractal dimension showed no statistical differences. L-PRF improved postoperative clinical parameters of pain, soft tissue healing, and periodontal condition, suggesting that it has a beneficial effect on preserving the alveolar ridge and accelerating the initial repair process.