Our objective was to conduct a systematic review and meta-analysis, comparing differences in clinical outcomes between either autologous or synthetic bone grafts in the operative management of tibial plateau fractures: a traumatic pattern of injury, associated with poor long-term functional prognosis. A structured search of MEDLINE, EMBASE, The Bone & Joint and CENTRAL databases from inception until 07/28/2021 was performed. Randomised, controlled, clinical trials that compared autologous and synthetic bone grafts in tibial plateau fractures were included. Preclinical studies, clinical studies in paediatric patients, pathological fractures, fracture non-union or chondral defects were excluded. Outcome data was assessed using the Risk of Bias 2 (ROB2) framework and synthesised in random-effect meta-analysis. Preferred Reported Items for Systematic Review and Meta-Analysis guidance was followed throughout. Six comparable studies involving 352 patients were identified from 3,078 records. Following ROB2 assessment, five studies (337 patients) were eligible for meta-analysis. Within these studies, more complex tibia plateau fracture patterns (Schatzker IV-VI) were predominant. Primary outcomes showed non-significant reductions in articular depression at immediate postoperative (mean difference −0.45mm, p=0.25, 95% confidence interval (95%CI): −1.21-0.31mm, I2=0%) and long-term (>6 months, standard mean difference −0.56, p=0.09, 95%CI: −1.20-0.08, I2=73%) follow-up in synthetic bone grafts. Secondary outcomes included mechanical alignment, limb functionality, defect site pain, occurrence of surgical site infections, secondary surgery, perioperative blood loss, and duration of surgery. Blood loss was lower (90.08ml, p<0.001, 95%CI: 41.49-138.67ml, I2=0%) and surgery was shorter (16.17minutes, p=0.04, 95%CI: 0.39-31.94minutes, I2=63%) in synthetic treatment groups. All other secondary measures were statistically comparable. Our findings supersede previous literature, demonstrating that synthetic bone grafts are non-inferior to autologous bone grafts, despite their perceived disadvantages (e.g. being biologically inert). In conclusion, surgeons should consider synthetic bone grafts when optimising peri-operative patient morbidity, particularly in complex tibial plateau fractures, where this work is most applicable.