Despite the remarkable progress in virtual surgical planning in the last few decades, which has made orthognathic surgery results more precise and predictable, there remains an unforeseeable risk of developing mandibular lower border defects after bilateral sagittal split osteotomy (BSSO). These defects can cause visible and palpable irregularities of the lower border of the mandible, thereby worsening the surgical result. The study aimed to evaluate the benefit of injectable platelet-rich fibrin (i-PRF) for contour defect modelling in orthognathic surgery in comparison to conventional orthognathic surgery. i-PRF was used to fill the osteotomy gap in BSSO aiming to stimulate bone tissue formation and reduce the risk of mandibular lower border defect formation. Additionally, the correlation between the concentration of the most important growth factors and interleukins in i-PRF and clinical outcomes of different patients was investigated. Also, the antibacterial activity of i-PRF was tested. Cone-beam computed tomography analysis demonstrated a statistically significant increase of bone volume in the BSSO vertical osteotomy gap when i-PRF was applied during surgery. The findings of the study support the use of an autologous biomaterial for BSSO, utilizing a simple preparation technique and application, while also contributing to a deeper understanding of i-PRF content and properties.