BACKGROUNDDried plasma is logistically superior for hemostasis management because it can be transported and stored under nonfrozen conditions and quickly reconstituted at the point of care, enabling prehospital administration. Velico Medical has developed a spray‐drying system to be integrated into routine blood center work streams for spray drying single donor plasma units. This study compared the quality of the spray‐dried plasma (on‐demand plasma [ODP]) with fresh frozen plasma (FFP).STUDY DESIGN AND METHODSODP units (n = 60) were manufactured from never frozen fresh plasma, which was pretreated with glycine–hydrochloric acid and stored at 1to 6°C. Paired aliquots were frozen and stored at −18°C or less. After 31 to 33 days, ODP samples were reconstituted with water for injection and comprehensively characterized in parallel with paired FFP. The quantities of plasma dried and rehydration fluid were predetermined, ensuring comparable total protein concentration in ODP and paired FFP.RESULTSODP is comparable to FFP in global coagulation function as assessed by activated partial thromboplastin time and prothrombin time and in clot formation evaluated by thrombelastography. Compared to FFP, ODP had greater than 80% levels of functional coagulation factors and related proteins and chemistry analytes except for Factor XIII (74%). Pretreatment mitigated cleavage of high‐molecular‐weight von Willebrand factor multimers by spray drying and resulted in 60% vWF:ristocetin cofactor activity in ODP compared to FFP.CONCLUSIONSODP demonstrates coagulation function comparable to that of FFP. The spray drying system can be implemented in blood centers and is capable of producing units of ODP.