The aim of this study was to provide an overview of massive transfusion in Chinese hospitals, identify the important indications for massive transfusion and corrective therapies based on clinical evidences and supporting experimental studies, and propose guidelines for the management of massive transfusion. This multi-region, multi-center retrospective study involved a Massive Blood Transfusion Coordination Group composed of 50 clinical experts specializing in blood transfusion, cardiac surgery, anesthesiology, obstetrics, general surgery, and medical statistics from 20 tertiary general hospitals across five regions in China. Data were collected for all patients, who received ≥ 10 U red blood cell transfusion within 24 hours in the participating hospitals from January 1 2009 to December 31 2010, including patient’s demographics, pre-, peri-, and post-operative clinical characteristics, laboratory test results before, during, and after transfusion, and patient mortality at post-transfusion and discharge. We also designed an in vitro hemodilution model to investigate the changes of blood coagulation indices during massive transfusion and the correction of coagulopathy through supplement blood components under different hemodilutions. The experimental data in combination with the clinical evidences were used to determine the optimal proportion and timing for blood component supplementation during massive transfusion. Based on the findings from the present study, together with an extensive review of domestic and international transfusion-related literature and consensus feedback from the 50 experts, we drafted the guidelines on massive blood transfusion that may help Chinese hospitals to develop standardized protocols for massive blood transfusion.