OBJECTIVE This study aimed to evaluate the effect of plasma transfusion before urgent hemostasis initiation on in-hospital mortality in hemodynamically unstable patients with severe trauma. METHODS This retrospective observational study of patients admitted to hospital between January 2011 and January 2019 grouped patients according to whether plasma transfusion was initiated before (Before group) or after (After group) hemostasis initiation. Patients with severe trauma who were unable to wait for plasma transfusion and had started hemostasis before the plasma infusion were excluded. We used multivariable logistic regression analysis to determine the effect of plasma transfusion before the initiation of urgent hemostasis on in-hospital mortality. RESULTS We included 47 and 73 patients in the Before and After groups, respectively. Blunt trauma was more common, and the D-dimer levels and Injury Severity Score were significantly higher in the Before group than in the After group (median D-dimer, 57.5 versus 38.1 μg/mL; P = 0.040; median Injury Severity Score, 50 versus 34; P < 0.001). Plasma given before hemostasis initiation was associated with significantly lower in-hospital mortality (adjusted odds ratio, 0.27; 95% confidence interval, 0.078-0.900; P = 0.033) in contrast with the total plasma volume given in the first 6 or 24 h. CONCLUSIONS Plasma transfusion before hemostasis initiation could be an important factor for improving outcomes in hemodynamically unstable patients with blunt trauma, high D-dimer levels, or a high Injury Severity Score.