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Background: Noncompressible hemorrhage is the leading cause of preventable death caused by hemorrhage on the battlefield. Currently, there are no hemostatic agents with the ability to control noncompressible hemorrhage. A wound stasis dressing based upon rapidly expanding cellulose minisponges (MS) was developed and tested in a lethal noncompressible model in swine, by fully transecting subclavian artery and vein. MS were compared with conventional hemostasis dressings, Combat Gauze (CG), in a randomized comparison., Methods: Sixteen 40-kg swine underwent transection of the subclavian artery and vein through a 4.5-cm aperture. After 30-second free bleeding, randomly selected MS or CG (n = 8 per group) were administered by an independent medical officer. The wound cavity was filled with either MS + no external pressure or one CG + one KERLIX gauze with 3 minutes of external pressure. One reapplication was allowed for CG. Mean arterial pressure was maintained at 60 mm Hg with 500-mL Hextend and lactated Ringer's solution intravenously administered up to a maximum of 10-L until study termination at 1 hour., Results: Mean pretreatment blood loss was similar for MS (719 mL) and CG (702 mL). Primary end points, namely, hemostasis at 4 minutes (MS, 75%; CG, 25%; p = 0.13), hemostasis at 60 minutes (MS, 100%; CG, 25%; p = 0.007), and survival at 60 minutes (MS, 100%; CG, 37.5%; p = 0.026), were improved with MS as were secondary end points, namely, total blood loss (MS, 118 mL; CG 1,242 mL; p = 0.021) and length of application time (MS, 25 seconds; CG, 420 seconds; p = 0.004)., Conclusion: The use of MS is a novel approach for the rapid, simple treatment of severe noncompressible hemorrhage, which provided statistically significant improvement in hemostasis and survival 60 minutes after injury and a large reduction in blood loss, resuscitation fluid requirement, and medic treatment time compared with conventional hemorrhage control dressings in a swine model.