Objectives <p>The purpose of this randomised, split-mouth clinical trial study is to investigate the effect of concentrated growth factors (CGF) on the healing of soft tissues and postoperative sequelae following the extraction of mesioangular impacted lower third molars in a split-mouth design.</p> Materials and methods <p>Twenty-five patients, systematically healthy, aged between 18 and 35, were subjected to bilateral lower third molar extraction (Class II, division B) at the oral surgery clinics in Damascus University, Syria, from October 2023 to July 2025. CGF was applied to one extraction site (test), and the opposite side served as a control (no treatment). Randomization was achieved through sealed envelopes, and the patients, outcome assessor, and data analyst were blinded. The main outcome was soft tissue healing, which was assessed by the Landry healing score at the 7th postoperative day. Secondary outcomes investigated were pain, which was assessed by the Visual Analog Scale throughout the 7th postoperative days, facial swelling, evaluated by the tape method at baseline, day 3, and day 7, and trismus by measuring the inter-incisal distance at baseline, third, and seventh postoperative days. Bonferroni correction was applied for repeated postoperative comparisons.</p> Results <p>At postoperative day 7, the CGF-treated sides exhibited superior healing compared with control sides (<i>p</i> = 0.008). Lower pain scores were observed in the test group during the first four postoperative days (unadjusted <i>p</i> &lt; 0.05); however, these differences did not remain statistically significant after Bonferroni correction. (<i>p</i> &gt; 0.05). Facial swelling was significantly lower in the CGF group on day 3 (<i>p</i> = 0.011) but not at day 7 (<i>p</i> = 0.247). No significant differences were found for trismus at any time-point (<i>p</i> = 0.260 &amp; 0.615).</p> Conclusion <p>The application of CGF to extraction sockets following surgical removal of mesioangular impacted mandibular third molars was associated with improved early soft tissue healing and reduced facial swelling at day 3. Although lower early postoperative pain scores were observed, these differences did not persist after multiplicity adjustment. No significant effects were observed for trismus or at later time points. CGF may represent a promising adjunctive local approach to support early postoperative recovery, particularly for enhancing soft tissue healing. Further research with larger samples and extended follow-up is recommended.</p> Clinical trial registration <p>Thailand Clinical Trial Registry (TCTR). Registration number (ID: TCTR20251102008). Registered on 02/11/2025 (retrospective registration).</p> <p>URL: (<a href="https://www.thaiclinicaltrials.org/show/TCTR2025110200">https://www.thaiclinicaltrials.org/show/TCTR20251102008</a>). </p>