Objective: To assess the benefits and safety of early human fibrinogen concentrate (FC) in postpartum haemorrhage (PPH) management. Design: Multicentre, double-blind, randomized placebo-controlled trial. Setting:30 French hospitals. Population: patients with persistent PPH after vaginal delivery requiring a switch from oxytocin to prostaglandins. Methods: Within 30 min after introduction of prostaglandins, patients received either 3 g FC or placebo. Main outcome measures: Failure as composite primary efficacy endpoint: at least 4 g/dL of haemoglobin decrease and/or transfusion of at least 2 units of packed red blood cells within 48h following investigational medicinal product administration. Secondary endpoints: PPH evolution, need for haemostatic procedures, and maternal morbidity-mortality within 6±2 weeks after delivery. Results: the intention-totreat analysis included 437 patients of which 224 received FC and 213 placebo. At inclusion, blood loss (877 ± 346mL) and plasma fibrinogen (FG) (4.1 ± 0.9g/L) were similar in both groups (mean ± SD). Failure rates were 40.0% and 42.4% in the FC and placebo groups, respectively (OR=0.99) after adjustment on centre and baseline FG; (95%CI: [0.66;1.47]; p=0.96). No significant differences in secondary efficacy outcomes were observed. The mean plasma FG was unchanged after 2 hours in the FC group and decreased by 0.56 g/L in the placebo group. No thromboembolic or other relevant adverse effects were reported in the FC group, versus two in the placebo group. Conclusions: Early and systematic administration of 3 g fibrinogen concentrate did not reduce blood loss, transfusion needs, and postpartum anaemia, but prevented plasma fibrinogen decrease without any subsequent thromboembolic events.