BACKGROUND: In severely injured trauma patients, hypofibrinoginaemia is associated with increased mortality. There is no evidence-based consensus for what constitutes optimal fibrinogen therapy, treatment dose or timing of administration. The aim of this systematic review was to evaluate the effects of early fibrinogen replacement, either cryoprecipitate or fibrinogen concentrate (FgC) on mortality, transfusion requirements and deep venous thrombosis (DVT). METHODS: A systematic search of studies was performed on MEDLINE, EMBASE and clinicaltrials.gov databases using standardised search criteria. All clinical studies which examined the use of either cryoprecipitate or FgC in patients with traumatic haemorrhage within 4 h of admission to hospital were included. Primary outcome was mortality (28-day, 30-day or in-hospital). Secondary outcomes were DVT incidence and blood component transfusions. A narrative synthesis was performed for all observational studies. Meta-analysis was completed for all included RCTs for mortality with pre-defined sub-group analysis of FgC and cryoprecipitate use. Grading of Recommendations Assessment, Development, and Evaluation was used to assess the quality of evidence. RESULTS: Overall, 1906 studies were screened with 12 studies included and five RCTs (all suitable for meta-analysis) totalling 1758 participants. Three RCTs reported FgC therapy, and two used cryoprecipitate. Four out of five RCTs examined empiric fibrinogen replacement for suspected traumatic haemorrhage. There was no difference in the primary outcome of mortality: early fibrinogen replacement (24%) vs control (25%), OR 1.03 (95% CI; 0.68-1.56). Subgroup analysis found no difference in outcome between the FgC and control: 18.1% vs 10.9% respectively, OR 1.99 (95% CI; 0.80-4.94). Similarly for cryoprecipitate, there was no difference in mortality between groups: cryoprecipitate (24.9%) vs control (26.1%), OR 0.71 (95% CI, 0.25-2.01). Reporting of transfusion data precluded meta-analysis. There was no difference in DVT incidence: fibrinogen replacement (3%) vs control (4%), OR 0.73 (0.43, 1.25). Overall, the quality of evidence was graded as low due to indirectness and imprecision. CONCLUSIONS: There is no association between early fibrinogen replacement and mortality, DVT or transfusion requirements. We found no superiority between FgC or cryoprecipitate. This systematic review highlights the urgent need for further RCTs to assess the efficacy of early fibrinogen replacement, preferred strategy (goal-directed vs empiric) as well as optimal therapeutic product for both patient outcome and cost effectiveness.